Modular Architecture of Metabolic Pathways Revealed by Conserved Sequences of Reactions
- Ai Muto
- ,
- Masaaki Kotera
- ,
- Toshiaki Tokimatsu
- ,
- Zenichi Nakagawa
- ,
- Susumu Goto
- , and
- Minoru Kanehisa
Abstract
The metabolic network is both a network of chemical reactions and a network of enzymes that catalyze reactions. Toward better understanding of this duality in the evolution of the metabolic network, we developed a method to extract conserved sequences of reactions called reaction modules from the analysis of chemical compound structure transformation patterns in all known metabolic pathways stored in the KEGG PATHWAY database. The extracted reaction modules are repeatedly used as if they are building blocks of the metabolic network and contain chemical logic of organic reactions. Furthermore, the reaction modules often correspond to traditional pathway modules defined as sets of enzymes in the KEGG MODULE database and sometimes to operon-like gene clusters in prokaryotic genomes. We identified well-conserved, possibly ancient, reaction modules involving 2-oxocarboxylic acids. The chain extension module that appears as the tricarboxylic acid (TCA) reaction sequence in the TCA cycle is now shown to be used in other pathways together with different types of modification modules. We also identified reaction modules and their connection patterns for aromatic ring cleavages in microbial biodegradation pathways, which are most characteristic in terms of both distinct reaction sequences and distinct gene clusters. The modular architecture of biodegradation modules will have a potential for predicting degradation pathways of xenobiotic compounds. The collection of these and many other reaction modules is made available as part of the KEGG database.
Introduction
Materials and Methods
Metabolic Pathway Database
Reactant Pairs
Reaction Class
Results
Similarity Grouping of RCLASS Entries
Extraction of Conserved RCLASS Sequence Patterns
length | no. of conserved patterns | no. of reactions included | coveragea |
---|---|---|---|
2 | 928 | 3479 | 0.599 |
3 | 770 | 2503 | 0.431 |
4 | 534 | 1662 | 0.286 |
5 | 338 | 1074 | 0.185 |
6 | 218 | 765 | 0.132 |
7 | 140 | 527 | 0.091 |
8 | 88 | 399 | 0.069 |
total | 3016 |
The ratio to 5805 reactions, the total number of reactions with RC assignment in the KEGG pathways.
RC module | description | length |
---|---|---|
RM001 | 2-oxocarboxylic acid chain extension by tricarboxylic acid pathway | 5 |
RM002 | caboxyl to amino conversion using protective N-acetyl group | 5 |
RM032 | caboxyl to amino conversion | 3 |
RM033 | branched chain addition | 4 |
RM030 | glucosinolate biosynthesis | 5 |
RM021 | fatty acid synthesis using malonyl-CoA | 4 |
RM020 | fatty acid synthesis using acetyl-CoA (reversal of beta oxidation) | 4 |
RM018 | beta oxidation in acyl-CoA degradation | 4 |
RM003 | methyl to carboxyl conversion on aromatic ring, aerobic | 3 |
RM004 | dihydroxylation of aromatic ring, type 1 (dioxygenase and dehydrogenase reactions) | 2 |
RM005 | dihydroxylation of aromatic ring, type 1a (dioxygenase and decarboxylating dehydrogenase reactions) | 2 |
RM006 | dihydroxylation of aromatic ring, type 2 (two monooxygenase reactions) | 2 |
RM008 | ortho-cleavage of catechol (beta-ketoadipate pathway) | 4 |
RM009 | meta-cleavage of catechol | 6 |
RM010 | dihydroxylation and meta-cleavage of aromatic ring, type 1 | 4 |
RM015 | oxidation of methyl group on aromatic ring, anaerobic | 6 |
RM016 | aromatic ring cleavage via beta oxidation, anaerobic | 3 |
RM025 | conversion of amino acid moiety to carboxyl group | 3 |
RM022 | nucleotide sugar biosynthesis, type 1 | 3 |
RM023 | nucleotide sugar biosynthesis, type 2 | 2 |
RM027 | hydroxylation and methylation motif | 2 |
See http://www.kegg.jp/kegg/reaction/rmodule.html for the full list of reaction modules.
General Characteristics of Reaction Modules
2-Oxocarboxylic Acid Chain Extension
RC module | pathway | overall reaction | RCLASS sequence |
---|---|---|---|
RM001 | citrate cycle (map00020) | oxaloacetate → 2-oxoglutarate | RC00067 RC00498 RC00618 RC00084+RC00626 |
lysine biosynthesis (map00300) | 2-oxoglutarate → 2-oxoadipate | RC00067 RC00498 RC00618 RC00114 | |
isoleucine biosynthesis (map00290) | pyruvate → 2-oxobutanoate | RC01205 RC00976 RC00977 RC00417 | |
leucine biosynthesis (map00290) | 2-oxoisovalerate → 2-oxoisocaproate | RC00470 RC01041 RC01046 RC00084+RC00577 | |
glucosinolate biosynthesis (map00966) | 2-oxo-4-methylthiobutanoate → 2-oxo-10-methylthiodecanoate | RC00067 RC00497 RC00114 (six repeats) | |
RM002 | lysine biosynthesis (map00300) | 2-aminoadipate → lysine | RC00064 RC00043 RC00684 RC00062 RC00064 |
arginine biosynthesis (map00330) | glutamate → ornithine | RC00064 RC00043 RC00684 RC00062 RC00064 | |
RM032 | ectoine biosynthesis (map00260) | aspartate → 2,4-diaminobutanoate | RC00043 RC00684 RC00062 |
RM033 | valine biosynthesis (map00290) | pyruvate → 2-oxoisovalerate | RC01192 RC00837 RC00726 RC00468 |
isoleucine biosynthesis (map00290) | 2-oxobutanoate → 3-methyl-2-oxopentanoate | RC01192 RC01726 RC00726 RC01714 | |
RM030 | glucosinolate biosynthesis (map00966) | homomethionine → glucoiberverin | RC02295 RC02210 RC02265 RC00882 RC00883 |
Modification of 2-Oxocarboxylic Acids
Reaction Modules Encoded in Enzyme Gene Clusters
RC module | overall reaction | KO module | gene cluster examplea |
---|---|---|---|
RM001 | oxaloacetate → 2-oxoglutarate | M00010 | (pfu) PF0203 PF0201 PF0202 |
2-oxoisovalerate → 2-oxoisocaproate | M00432 | (pfu) PF0937 PF0938+PF0939 PF0940 | |
pyruvate → 2-oxobutanoate | M00535 | (bth) BT_1858 BT_1860+BT_1859 BT_1857 | |
RM002 | 2-aminoadipate → lysine | M00028 | (bsu) BSU11200 BSU11210+BSU11190 BSU11220 |
glutamate → ornithine | M00031 | (ttr) Tter_0315+Tter_0316 Tter_0320 Tter_0319 Tter_0321 Tter_0317 |
KEGG organism codes are shown in parentheses: pfu (T00075), Pyrococcus furiosus DSM 3638; bth (T00122), Bacteroides thetaiotaomicrometer VPI-5482; bsu (T00010), Bacillus subtilis 168; ttr (T01134), Thermobaculum terrenum ATCC BAA-798.
Fatty Acid Synthesis and Beta Oxidation
Aromatic Ring Cleavage in Microbial Biodegradation Pathways
RC module | KO module | overall reaction |
---|---|---|
RM003 | M00538 | toluene → benzoate |
M00537 | o-xylene → o-methylbenzoate | |
M00419 | p-cymene → p-cumate | |
RM004 | M00547 | benzoate → catechol |
RM005 | M00551 | benzoate → catechol |
RM006 | M00548 | benzene → catechol |
RM008 | M00568 | catechol → 3-oxoadipate |
RM009 | M00569 | catechol → pyruvate + acetaldehyde |
RM010 | M00539 | p-cumate → 2-oxopent-4-enoate + methylpropanoate |
M00543 | biphenyl → 2-oxopent-4-enoate + benzoate | |
RM015 | M00418 | toluene → benzoyl-CoA |
Discussion
EC subsubclass | no. of RC entries | enzymes involved |
---|---|---|
1.14.13 | 150 | monooxygenases |
4.2.1 | 129 | hydratases/dehydratases, terpene cyclases (hydrating) |
1.1.1 | 117 | alcohol:NAD(P)+ dehydrogenases |
4.2.3 | 86 | phospho-lyases, terpene cyclases (diphosphate-eliminating) |
1.14.14 | 83 | monooxygenases |
2.1.1 | 79 | methyltransferases |
1.13.11 | 72 | dioxygenases |
1.3.1 | 68 | saturases/desaturases |
4.1.1 | 65 | carboxylases/decarboxylases |
2.5.1 | 60 | prenyltransferases, 1-carboxyvinyltransferases, aminocarboxyethyltransferases, aminocarboxypropyltransferases, adenosyltransferases |
Supporting Information
KEGG atom types, RDM patterns, fingerprint representation, and similarity scoring of RC entries (Methods); tricarboxylic acid pathway (Figure S1); glucosinolate biosynthesis pathway (Figure S2); carboxyl to amino conversion (Figure S3); fatty acid biosynthesis (Figure S4); beta oxidation (Figure S5); methyl to carboxyl conversion on aromatic ring (Figure S6); amino to carboxyl conversion (Figure S7); nucleotide sugar biosynthesis (Figure S8); phenylpropanoid biosynthesis (Figure S9); and classification of monooxygenases (Figure S10). This information is available free of charge via the Internet at http://pubs.acs.org.
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Acknowledgment
We thank Dr. Nicolas Joannin for critical reading of the manuscript. This work was supported by the Japan Science and Technology Agency. Computational resources were provided by the Bioinformatics Center, Institute for Chemical Research, Kyoto University.
References
This article references 28 other publications.
-
1Bono, H.; Ogata, H.; Goto, S.; Kanehisa, M. Reconstruction of amino acid biosynthesis pathways from the complete genome sequence Genome Res. 1998, 8, 203– 210Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXitlWksrg%253D&md5=fc164a7deefa6b03be0c5512d7229545Reconstruction of amino acid biosynthesis pathways from the complete genome sequenceBono, Hidemasa; Ogata, Hiroyuki; Goto, Susumu; Kanehisa, MinoruGenome Research (1998), 8 (3), 203-210CODEN: GEREFS; ISSN:1088-9051. (Cold Spring Harbor Laboratory Press)The complete genome sequence of an organism contains information that has not been fully utilized in the current prediction methods of gene functions, which are based on piece-by-piece similarity searches of individual genes. A method is presented a method that utilizes a higher level information of mol. pathways to reconstruct a complete functional unit from a set of genes. Specifically, a genome-by-genome comparison is first made for identifying enzyme genes and assigning EC nos., which is followed by the reconstruction of selected portions of the metabolic pathways by use of the reconstructed pathway is an indicator of the correctness of the initial gene function assignment. This feature has become possible because of efforts to computerize the current knowledge of metabolic pathways under the KEGG project. The biosynthesis pathway of all 20 amino acids were completely reconstructed in Escherichia coli, Haemophilus influenzae, and Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as well, although it was necessary to assume wilder substrate specificity for aspartate aminotransferases.
-
2Galperin, M. Y.; Koonin, E. V. Functional genomics and enzyme evolution. Homologous and analogous enzymes encoded in microbial genomes Genetica 1999, 106, 159– 170Google ScholarThere is no corresponding record for this reference.
-
3Dandekar, T.; Schuster, S.; Snel, B.; Huynen, M.; Bork, P. Pathway alignment: application to the comparative analysis of glycolytic enzymes Biochem. J. 1999, 343, 115– 124Google ScholarThere is no corresponding record for this reference.
-
4Forst, C. V.; Schulten, K. Evolution of metabolisms: a new method for the comparison of metabolic pathways using genomics information J. Comput. Biol. 1999, 6, 343– 360Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXns1enuro%253D&md5=81eea3db60585f2a55d9f79c09274c4eEvolution of metabolisms: a new method for the comparison of metabolic pathways using genomics informationForst, Christian V.; Schulten, KlausJournal of Computational Biology (1999), 6 (3/4), 343-360CODEN: JCOBEM; ISSN:1066-5277. (Mary Ann Liebert, Inc.)The abundance of information provided by completely sequenced genomes defines a starting point for new insights in the multilevel organization of organisms and their evolution. At the lowest level enzymes and other protein complexes are formed by aggregating multiple polypeptides. At a higher level enzymes group conceptually into metabolic pathways as part of a dynamic information-processing system, and substrates are processed by enzymes yielding other substrates. A method based on a combination of sequence information with graph topol. of the underlying pathway is presented. With this approach pathways of different organisms are related to each other by phylogenetic anal., extending conventional phylogenetic anal. of individual enzymes. The new method is applied to pathways related to electron transfer and to the Krebs citric acid cycle. In addn. to providing a more comprehensive understanding of similarities and differences between organisms, this method indicates different evolutionary rates between substrates and enzymes.
-
5Ogata, H.; Fujibuchi, W.; Goto, S.; Kanehisa, M. A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters Nucleic Acids Res. 2000, 28, 4021– 4028Google ScholarThere is no corresponding record for this reference.
-
6Tohsato, Y.; Matsuda, H.; Hashimoto, A. A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchy Proc. Int. Conf. Intell. Syst. Mol. Biol. 2000, 8, 376– 383Google Scholar6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3M7gt1artQ%253D%253D&md5=af098d7d4bb217e243aceb490a1afd59A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchyTohsato Y; Matsuda H; Hashimoto AProceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology (2000), 8 (), 376-83 ISSN:1553-0833.In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Comparative analyses of the metabolic pathways formed by such reactions give important information on their evolution and on pharmacological targets (Dandekar et al. 1999). Each of the enzymes that constitute a pathway is classified according to the EC (Enzyme Commission) numbering system, which consists of four sets of numbers that categorize the type of the chemical reaction catalyzed. In this study, we consider that reaction similarities can be expressed by the similarities between EC numbers of the respective enzymes. Therefore, in order to find a common pattern among pathways, it is desirable to be able to use the functional hierarchy of EC numbers to express the reaction similarities. In this paper, we propose a multiple alignment algorithm utilizing information content that is extended to symbols having a hierarchical structure. The effectiveness of our method is demonstrated by applying the method to pathway analyses of sugar, DNA and amino acid metabolisms.
-
7Pinter, R. Y.; Rokhlenko, O.; Yeger-Lotem, E.; Ziv-Ukelson, M. Alignment of metabolic pathways Bioinformatics 2005, 21, 3401– 3408Google ScholarThere is no corresponding record for this reference.
-
8Wernicke, S.; Rasche, F. Simple and fast alignment of metabolic pathways by exploiting local diversity Bioinformatics 2007, 23, 1978– 1985Google ScholarThere is no corresponding record for this reference.
-
9Tohsato, Y.; Nishimura, Y. Reaction similarities focusing substructure changes of chemical compounds and metabolic pathway alignments Inf. Media Technol. 2009, 4, 390– 399Google ScholarThere is no corresponding record for this reference.
-
10Ay, Y.; Kellis, M.; Kahveci, T. SubMAP: aligning metabolic pathways with subnetwork mappings J. Comput. Biol. 2011, 18, 219– 235Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjtlSjt7g%253D&md5=f9f9250ab813c22517f669e458a4b0bbSubMAP: aligning metabolic pathways with subnetwork mappingsAy, Ferhat; Kellis, Manolis; Kahveci, TamerJournal of Computational Biology (2011), 18 (3), 219-235CODEN: JCOBEM; ISSN:1557-8666. (Mary Ann Liebert, Inc.)We consider the problem of aligning two metabolic pathways. Unlike traditional approaches, we do not restrict the alignment to one-to-one mappings between the mols. (nodes) of the input pathways (graphs). We follow the observation that, in nature, different organisms can perform the same or similar functions through different sets of reactions and mols. The no. and the topol. of the mols. in these alternative sets often vary from one organism to another. With the motivation that an accurate biol. alignment should be able to reveal these functionally similar mol. sets across different species, we develop an algorithm that first measures the similarities between different nodes using a mixt. of homol. and topol. similarity. We combine the two metrics by employing an eigenvalue formulation. We then search for an alignment between the two input pathways that maximizes a similarity score, evaluated as the sum of the similarities of the mapped subnetworks of size at most a given integer k, and also does not contain any conflicting mappings. Here we prove that this maximization is NP-hard by a redn. from the max. wt. independent set (MWIS) problem. We then convert our problem to an instance of MWIS and use an efficient vertex-selection strategy to ext. the mappings that constitute our alignment. We name our algorithm SubMAP (Subnetwork Mappings in Alingment of Pathways). We evaluate its accuracy and performance on real datasets. Our empirical results demonstrate that SubMAP can identify biol. relevant mappings that are missed by traditional alignment methods. Furthermore, we observe that SubMAP is scalable for metabolic pathways of arbitrary topol., including searching for a query pathway of size 70 against the complete KEGG database of 1,842 pathways.
-
11Kanehisa, M.; Goto, S.; Sato, Y.; Furumichi, M.; Tanabe, M. KEGG for integration and interpretation of large-scale molecular data sets Nucleic Acids Res. 2012, 40, D109– D114Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs12htbrO&md5=d234c2f8945fbec1d3767e11fa96710bKEGG for integration and interpretation of large-scale molecular data setsKanehisa, Minoru; Goto, Susumu; Sato, Yoko; Furumichi, Miho; Tanabe, MaoNucleic Acids Research (2012), 40 (D1), D109-D114CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/ or http://www.kegg.jp/) is a database resource that integrates genomic, chem. and systemic functional information. In particular, gene catalogs from completely sequenced genomes are linked to higher-level systemic functions of the cell, the organism and the ecosystem. Major efforts have been undertaken to manually create a knowledge base for such systemic functions by capturing and organizing exptl. knowledge in computable forms; namely, in the forms of KEGG pathway maps, BRITE functional hierarchies and KEGG modules. Continuous efforts have also been made to develop and improve the cross-species annotation procedure for linking genomes to the mol. networks through the KEGG Orthol. system. Here we report KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets. We also report a variant of the KEGG mapping procedure to extend the knowledge base, where different types of data and knowledge, such as disease genes and drug targets, are integrated as part of the KEGG mol. networks. Finally, we describe recent enhancements to the KEGG content, esp. the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics.
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12Kotera, M.; Okuno, Y.; Hattori, M.; Goto, S.; Kanehisa, M. Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions J. Am. Chem. Soc. 2004, 126, 16487– 16498Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtVCisb%252FM&md5=901f1cbf5fc79870f63fcca0a9ff2004Computational Assignment of the EC Numbers for Genomic-Scale Analysis of Enzymatic ReactionsKotera, Masaaki; Okuno, Yasushi; Hattori, Masahiro; Goto, Susumu; Kanehisa, MinoruJournal of the American Chemical Society (2004), 126 (50), 16487-16498CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The EC (Enzyme Commission) nos. represent a hierarchical classification of enzymic reactions, but they are also commonly utilized as identifiers of enzymes or enzyme genes in the anal. of complete genomes. This duality of the EC nos. makes it possible to link the genomic repertoire of enzyme genes to the chem. repertoire of metabolic pathways, the process called metabolic reconstruction. Unfortunately, there are numerous reactions known to be present in various pathways, but they will never get EC nos. because the EC no. assignment requires published articles on full characterization of enzymes. Here we report a computerized method to automatically assign the EC nos. up to the sub-subclasses, i.e., without the fourth serial no. for substrate specificity, given pairs of substrates and products. The method is based on a new classification scheme of enzymic reactions, named the RC (reaction classification) no. Each reaction in the current dataset of the EC nos. is first decompd. into reactant pairs. Each pair is then structurally aligned to identify the reaction center, the matched region, and the difference region. The RC no. represents the conversion patterns of atom types in these three regions. We examd. the correspondence between computationally assigned RC nos. and manually assigned EC nos. by the jackknife cross-validation test and found that the EC sub-subclasses could be assigned with the accuracy of about 90%. Furthermore, we examd. the correlation with genomic information as represented by the KEGG ortholog clusters (OC) and confirmed that the RC nos. are correlated not only with elementary reaction mechanisms but also with protein families.
-
13McDonald, A. G.; Boyce, S.; Tipton, K. F. ExplorEnz: the primary source of the IUBMB enzyme list Nucleic Acids Res. 2009, 37, D593– D597Google ScholarThere is no corresponding record for this reference.
-
14Hattori, M.; Okuno, Y.; Goto, S.; Kanehisa, M. Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways J. Am. Chem. Soc. 2003, 125, 11853– 11865Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnt1Knuro%253D&md5=6083bca700feacbf75695fdbe8c79521Development of a Chemical Structure Comparison Method for Integrated Analysis of Chemical and Genomic Information in the Metabolic PathwaysHattori, Masahiro; Okuno, Yasushi; Goto, Susumu; Kanehisa, MinoruJournal of the American Chemical Society (2003), 125 (39), 11853-11865CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Cellular functions result from intricate networks of mol. interactions, which involve not only proteins and nucleic acids but also small chem. compds. Here we present an efficient algorithm for comparing two chem. structures of compds., where the chem. structure is treated as a graph consisting of atoms as nodes and covalent bonds as edges. On the basis of the concept of functional groups, 68 atom types (node types) are defined for carbon, nitrogen, oxygen, and other at. species with different environments, which has enabled detection of biochem. meaningful features. Maximal common subgraphs of two graphs can be found by searching for maximal cliques in the assocn. graph, and we have introduced heuristics to accelerate the clique finding and to detect optimal local matches (simply connected common subgraphs). Our procedure was applied to the comparison and clustering of 9383 compds., mostly metabolic compds., in the KEGG/LIGAND database. The largest clusters of similar compds. were related to carbohydrates, and the clusters corresponded well to the categorization of pathways as represented by the KEGG pathway map nos. When each pathway map was examd. in more detail, finer clusters could be identified corresponding to subpathways or pathway modules contg. continuous sets of reaction steps. Furthermore, it was found that the pathway modules identified by similar compd. structures sometimes overlap with the pathway modules identified by genomic contexts, namely, by operon structures of enzyme genes.
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15Jensen, R. A. Enzyme recruitment in evolution of new function Annu. Rev. Microbiol. 1976, 30, 409– 425Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE28XlvVyitLs%253D&md5=c28c95884851c8d4336cb1359898f148Enzyme recruitment in evolution of new functionJensen, Roy A.Annual Review of Microbiology (1976), 30 (), 409-25CODEN: ARMIAZ; ISSN:0066-4227.A review with 96 refs., emphasizing the prospects for defining evolutionary relations between enzymes that coexist in the same organism but that no longer serve the same function.
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16Horie, A.; Tomita, T.; Saiki, A.; Kono, H.; Taka, H.; Mineki, R.; Fujimura, T.; Nishiyama, C.; Kuzuyama, T.; Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus Nat. Chem. Biol. 2009, 5, 673– 679Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXoslensLs%253D&md5=e9bfcc9ed50f6a0b7e726a9e71fa2f8dDiscovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilusHorie, Akira; Tomita, Takeo; Saiki, Asako; Kono, Hidetoshi; Taka, Hikari; Mineki, Reiko; Fujimura, Tsutomu; Nishiyama, Chiharu; Kuzuyama, Tomohisa; Nishiyama, MakotoNature Chemical Biology (2009), 5 (9), 673-679CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)Although the latter portion of lysine biosynthesis, the conversion of α-aminoadipate (AAA) to lysine, in Thermus thermophilus is similar to the latter portion of arginine biosynthesis, enzymes homologous to ArgA and ArgJ are absent from the lysine pathway. Because ArgA and ArgJ are known to modify the amino group of glutamate to avoid intramol. cyclization of intermediates, their absence suggests that the pathway includes an alternative N-modification system. We reconstituted the conversion of AAA to lysine and found that the amino group of AAA is modified by attachment to the γ-carboxyl group of the C-terminal Glu54 of a small protein, LysW; that the side chain of AAA is converted to the lysyl side chain while still attached to LysW; and that lysine is subsequently liberated from the LysW-lysine fusion. The fact that biosynthetic enzymes recognize the acidic globular domain of LysW indicates that LysW acts as a carrier protein or protein scaffold for the biosynthetic enzymes. This study thus reveals the previously unknown function of a small protein in primary metab.
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17Maeder, D. L.; Weiss, R. B.; Dunn, D. M.; Cherry, J. L.; González, J. M.; DiRuggiero, J.; Robb, F. T. Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P. horikoshii inferred from complete genomic sequences Genetics 1999, 152, 1299– 1305Google ScholarThere is no corresponding record for this reference.
-
18Pelletier, D. A.; Harwood, C. S. 2-Hydroxycyclohexanecarboxyl coenzyme A dehydrogenase, an enzyme characteristic of the anaerobic benzoate degradation pathway used by Rhodopseudomonas palustris J. Bacteriol. 2000, 182, 2753– 2760Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXivFKqs7s%253D&md5=b1c35611674df5eaac568d4f53dc340b2-Hydroxycyclohexanecarboxyl coenzyme A dehydrogenase, an enzyme characteristic of the anaerobic benzoate degradation pathway used by Rhodopseudomonas palustrisPelletier, Dale A.; Harwood, Caroline S.Journal of Bacteriology (2000), 182 (10), 2753-2760CODEN: JOBAAY; ISSN:0021-9193. (American Society for Microbiology)A gene, badH, whose predicted product is a member of the short-chain dehydrogenase/reductase family of enzymes, was recently discovered during studies of anaerobic benzoate degrdn. by the photoheterotrophic bacterium Rhodopseudomonas palustris. Purified histidine-tagged BadH protein catalyzed the oxidn. of 2-hydroxycyclohexanecarboxyl CoA (2-hydroxychc-CoA) to 2-ketocyclohexanecarboxyl-CoA. These compds. are proposed intermediates of a series of three reactions that are shared by the pathways of cyclohexanecarboxylate and benzoate degrdn. used by R. palustris. The 2-hydroxychc-CoA dehydrogenase activity encoded by badH was dependent on the presence of NAD+; no activity was detected with NADP+ as a cofactor. The dehydrogenase activity was not sensitive to oxygen. The enzyme has apparent Km values of 10 and 200 μM for 2-hydroxychc-CoA and NAD+, resp. Western blot anal. with antisera raised against purified His-BadH identified a 27-kDa protein that was present in benzoate- and cyclohexanecarboxylate-grown but not in succinate-grown R. palustris cell exts. The active form of the enzyme is a homotetramer. BadH was detd. to be the first gene in an operon, termed the cyclohexanecarboxylate degrdn. operon, contg. genes required for both benzoate and cyclohexanecarboxylate degrdn. A nonpolar R. palustris badH mutant was unable to grow on benzoate or cyclohexanecarboxylate but had wild-type growth rates on succinate. Cells blocked in expression of the entire cyclohexanecarboxylate degrdn. operon excreted cyclohex-1-ene-1-carboxylate into the growth medium when given benzoate. This confirms that cyclohex-1-ene-1-carboxyl-CoA is an intermediate of anaerobic benzoate degrdn. by R. palustris. This compd. had previously been shown not to be formed by Thauera aromatica, a denitrifying bacterium that degrades benzoate by a pathway that is slightly different from the R. palustris pathway. 2-Hydroxychc-CoA dehydrogenase does not participate in anaerobic benzoate degrdn. by T. aromatica and thus may serve as a useful indicator of an R. palustris-type benzoate degrdn. pathway.
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19Harwood, C. S.; Parales, R. E. The beta-ketoadipate pathway and the biology of self-identity Annu. Rev. Microbiol. 1996, 50, 553– 590Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XmtFGhtro%253D&md5=69dfa001f3f6c320d33b0c788a1e0aa1The β-ketoadipate pathway and the biology of self-identityHarwood, Caroline S.; Parales, Rebecca E.Annual Review of Microbiology (1996), 50 (), 553-590CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews)A review with 163 refs. The β-ketoadipate pathway is a chromosomally encoded convergent pathway for arom. compd. degrdn. that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compds. including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to β-ketoadipate. The other branch converts catechol, generated from various arom. hydrocarbons, amino aroms., and lignin monomers, also to β-ketoadipate. Two addnl. steps accomplish the conversion of β-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the β-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degrdn. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic β-ketoadipate pathway. In the face of enzyme conservation, the β-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isoenzymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to β-ketoadipate pathway-assocd. arom. compds. The presence and versatility of transport systems encoded by β-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the β-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.
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20Rabus, R.; Kube, M.; Heider, J.; Beck, A.; Heitmann, K.; Widdel, F.; Reinhardt, R. The genome sequence of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1 Arch. Microbiol. 2005, 183, 27– 36Google ScholarThere is no corresponding record for this reference.
-
21Lee, S. H.; Jin, H. M.; Lee, H. J.; Kim, J. M.; Jeon, C. O. Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59 J. Bacteriol. 2012, 194, 544Google Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsFWmtQ%253D%253D&md5=2f3354e3bf9b91c99a7ff36820c18801Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59Lee, Seung Hyeon; Jin, Hyun Mi; Lee, Hyo Jung; Kim, Jeong Myeong; Jeon, Che OkJournal of Bacteriology (2012), 194 (2), 544CODEN: JOBAAY; ISSN:0021-9193. (American Society for Microbiology)Pseudoxanthomonas spadix BD-a59, able to metabolize all six BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p-xylene) compds., was isolated from gasoline-contaminated sediment. This report presents the complete 3.45-Mb genome sequence and annotation of strain BD-a59. These advance the understanding of strain BD-a59's genomic properties and pollutant metabolic versatility. The complete genome sequence (3,452,554 bp, 3150 predicted protein-coding sequences) is deposited in GenBank/EMBL/DDBJ with accession no. CP003093.
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22Papin, J. A.; Reed, J. L.; Palsson, B. O. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks Trends Biochem. Sci. 2004, 29, 641– 647Google ScholarThere is no corresponding record for this reference.
-
23Ravasz, E.; Somera, A. L.; Mongru, D. A.; Oltvai, Z. N.; Barabási, A. L. Hierarchical organization of modularity in metabolic networks Science 2002, 297, 1551– 1555Google ScholarThere is no corresponding record for this reference.
-
24Schuster, S.; Pfeiffer, T.; Moldenhauer, F.; Koch, I.; Dandekar, T. Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae Bioinformatics 2002, 18, 351– 361Google ScholarThere is no corresponding record for this reference.
-
25Yamada, T.; Kanehisa, M.; Goto, S. Extraction of phylogenetic network modules from the metabolic network BMC Bioinf. 2006, 7, 130Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD28vhsFekug%253D%253D&md5=c8b1ec61a032234c2a5f2d0cb8f159a9Extraction of phylogenetic network modules from the metabolic networkYamada Takuji; Kanehisa Minoru; Goto SusumuBMC bioinformatics (2006), 7 (), 130 ISSN:.BACKGROUND: In bio-systems, genes, proteins and compounds are related to each other, thus forming complex networks. Although each organism has its individual network, some organisms contain common sub-networks based on function. Given a certain sub-network, the distribution of organisms common to it represents the diversity of its function. RESULTS: We extracted such "common" sub-networks, defined as "phylogenetic network modules," using phylogenetic profiles and cluster analysis. The enzymes in the same "phylogenetic network module" have similar phylogenetic profiles and related functions. These modules are shown to be phylogenetic building blocks. Furthermore, the network of the modules illustrated hierarchical feature as well as the network of enzymes involved in the metabolism. CONCLUSION: We conclude that phylogenetic network modules are evolutionary conserved functional units in the metabolic network. We claim that our concept of phylogenetic modules provides a more accurate understanding of the evolution of biological networks.
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26Horowitz, N. H. On the evolution of biochemical synthesis Proc. Natl. Acad. Sci USA 1945, 31, 153– 157Google ScholarThere is no corresponding record for this reference.
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27Ycas, M. On earlier states of the biochemical system J. Theor. Biol. 1974, 44, 145– 160Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2cXhtFOhur4%253D&md5=cfea1aa54c197fed53fa8f37dd1eb672Earlier states of the biochemical systemYcas, MartynasJournal of Theoretical Biology (1974), 44 (1), 145-60CODEN: JTBIAP; ISSN:0022-5193.Similarities between essential enzymes indicate homology and therefore origin from a smaller no. of ancestral genes, but there are also indications that the immediately preceding biochem. system was of about the same complexity as the present one. In order to maintain function with a smaller no. of enzymes, earlier enzymes must have been less specific, catalyzing classes of reactions. Lower specificity also resulted in ambiguous translation, each cistron producing a family of related proteins. Though individual protein mols. need not have been less specific, each family as a whole functioned as a catalyst of lower specificity. The no. of kinds of amino acids incorporated into proteins may have been larger than at present. The evidence supporting this, some of its implications, and the kinds of addnl. data that would be useful in such problems are discussed.
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28Chu, H. Y.; Wegel, E.; Osbourn, A. From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants Plant J. 2011, 66, 66– 79Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsVKnurc%253D&md5=991bd057a438dbea360c325fe69559e4From hormones to secondary metabolism: The emergence of metabolic gene clusters in plantsChu, Hoi Yee; Wegel, Eva; Osbourn, AnnePlant Journal (2011), 66 (1), 66-79CODEN: PLJUED; ISSN:0960-7412. (Wiley-Blackwell)A review. Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently, it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defense compds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge.
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- Aman C. Kaushik, Sanjay Kumar, Dong Q. Wei, Shakti Sahi. Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes. Frontiers in Chemistry 2018, 6 https://doi.org/10.3389/fchem.2018.00023
- Sinosh Skariyachan, Meghna Manjunath, Apoorva Shankar, Nikhil Bachappanavar, Amulya A. Patil. Application of Novel Microbial Consortia for Environmental Site Remediation and Hazardous Waste Management Toward Low- and High-Density Polyethylene and Prioritizing the Cost-Effective, Eco-friendly, and Sustainable Biotechnological Intervention. 2018, 1-48. https://doi.org/10.1007/978-3-319-58538-3_9-1
- Minoru Kanehisa, Miho Furumichi, Mao Tanabe, Yoko Sato, Kanae Morishima. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Research 2017, 45 (D1) , D353-D361. https://doi.org/10.1093/nar/gkw1092
- Minoru Kanehisa. KEGG GLYCAN. 2017, 177-193. https://doi.org/10.1007/978-4-431-56454-6_9
- Icxa Khandelwal, Aditi Sharma, Pavan Kumar Agrawal, Rahul Shrivastava. Bioinformatics Database Resources. 2017, 45-90. https://doi.org/10.4018/978-1-5225-1871-6.ch004
- Kazuhiro Takemoto, Masato Ii, Satoshi S. Nishizuka. Importance of metabolic rate to the relationship between the number of genes in a functional category and body size in Peto's paradox for cancer. Royal Society Open Science 2016, 3 (9) , 160267. https://doi.org/10.1098/rsos.160267
- Jennifer H. Wisecaver, William G. Alexander, Sean B. King, Chris Todd Hittinger, Antonis Rokas. Dynamic Evolution of Nitric Oxide Detoxifying Flavohemoglobins, a Family of Single-Protein Metabolic Modules in Bacteria and Eukaryotes. Molecular Biology and Evolution 2016, 33 (8) , 1979-1987. https://doi.org/10.1093/molbev/msw073
- Daniel Cerqueda-García, Luisa I. Falcón. Metabolic potential of microbial mats and microbialites: Autotrophic capabilities described by an in silico stoichiometric approach from shared genomic resources. Journal of Bioinformatics and Computational Biology 2016, 14 (04) , 1650020. https://doi.org/10.1142/S0219720016500207
- Minoru Kanehisa, Yoko Sato, Masayuki Kawashima, Miho Furumichi, Mao Tanabe. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Research 2016, 44 (D1) , D457-D462. https://doi.org/10.1093/nar/gkv1070
- Minoru Kanehisa. KEGG Bioinformatics Resource for Plant Genomics and Metabolomics. 2016, 55-70. https://doi.org/10.1007/978-1-4939-3167-5_3
- Jinzeng Wang, Haiyun Wang. Integrative Biological Databases. 2016, 295-307. https://doi.org/10.1007/978-94-017-7543-4_11
- Kazuhiro Takemoto. Habitat variability does not generally promote metabolic network modularity in flies and mammals. Biosystems 2016, 139 , 46-54. https://doi.org/10.1016/j.biosystems.2015.12.004
- Masaaki Kotera, Susumu Goto. Metabolic pathway reconstruction strategies for central metabolism and natural product biosynthesis. Biophysics and Physicobiology 2016, 13 (0) , 195-205. https://doi.org/10.2142/biophysico.13.0_195
- Maria Sorokina, Claudine Medigue, David Vallenet. A new network representation of the metabolism to detect chemical transformation modules. BMC Bioinformatics 2015, 16 (1) https://doi.org/10.1186/s12859-015-0809-4
- Kazuhiro Takemoto, Yuko Kawakami. The proportion of genes in a functional category is linked to mass-specific metabolic rate and lifespan. Scientific Reports 2015, 5 (1) https://doi.org/10.1038/srep10008
- Aman Chandra Kaushik, Shakti Sahi. Boolean network model for GPR142 against Type 2 diabetes and relative dynamic change ratio analysis using systems and biological circuits approach. Systems and Synthetic Biology 2015, 9 (1-2) , 45-54. https://doi.org/10.1007/s11693-015-9163-0
- M. Uchihashi, I. L. Bergin, C. M. Bassis, S. A. Hashway, D. Chai, J. D. Bell. Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons ( Papio anubis ). American Journal of Primatology 2015, 77 (5) , 563-578. https://doi.org/10.1002/ajp.22378
- Masaaki KOTERA, Susumu GOTO. Metabolome-scale Prediction of Intermediate Compounds in Multistep Metabolic Pathways with a Recursive Supervised Approach. Seibutsu Butsuri 2015, 55 (3) , 160-163. https://doi.org/10.2142/biophys.55.160
- Masaaki Kotera, Yosuke Nishimura, Zen-Ichi Nakagawa, Ai Muto, Yuki Moriya, Shinobu Okamoto, Shuichi Kawashima, Toshiaki Katayama, Toshiaki Tokimatsu, Minoru Kanehisa, Susumu Goto. PIERO ontology for analysis of biochemical transformations: Effective implementation of reaction information in the IUBMB enzyme list. Journal of Bioinformatics and Computational Biology 2014, 12 (06) , 1442001. https://doi.org/10.1142/S0219720014420013
- Kazuhiro Takemoto. Metabolic networks are almost nonfractal: A comprehensive evaluation. Physical Review E 2014, 90 (2) https://doi.org/10.1103/PhysRevE.90.022802
- Anna Zhukova, David James Sherman. Knowledge-based Generalization of Metabolic Models. Journal of Computational Biology 2014, 21 (7) , 534-547. https://doi.org/10.1089/cmb.2013.0143
- Editho S. Giray, Geoffrey A. Solano, Ma. Constancia O. Carillo, Jhoirene B. Clemente, Henry N. Adorna. Building phylogenetic trees from frequent subgraph mining techniques on reaction hypergraphs. 2014, 179-184. https://doi.org/10.1109/IISA.2014.6878771
- Masaaki Kotera, Yasuo Tabei, Yoshihiro Yamanishi, Ai Muto, Yuki Moriya, Toshiaki Tokimatsu, Susumu Goto. Metabolome-scale prediction of intermediate compounds in multistep metabolic pathways with a recursive supervised approach. Bioinformatics 2014, 30 (12) , i165-i174. https://doi.org/10.1093/bioinformatics/btu265
- Anna Zhukova, David J. Sherman. Knowledge-based generalization of metabolic networks: A practical study. Journal of Bioinformatics and Computational Biology 2014, 12 (02) , 1441001. https://doi.org/10.1142/S0219720014410017
- Martina Klünemann, Melanie Schmid, Kiran Raosaheb Patil. Computational tools for modeling xenometabolism of the human gut microbiota. Trends in Biotechnology 2014, 32 (3) , 157-165. https://doi.org/10.1016/j.tibtech.2014.01.005
- George H. Greene, Kriston L. McGary, Antonis Rokas, Jason C. Slot. Ecology Drives the Distribution of Specialized Tyrosine Metabolism Modules in Fungi. Genome Biology and Evolution 2014, 6 (1) , 121-132. https://doi.org/10.1093/gbe/evt208
- Minoru Kanehisa, Susumu Goto, Yoko Sato, Masayuki Kawashima, Miho Furumichi, Mao Tanabe. Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Research 2014, 42 (D1) , D199-D205. https://doi.org/10.1093/nar/gkt1076
- Toshiaki Katayama, Mark D Wilkinson, Kiyoko F Aoki-Kinoshita, Shuichi Kawashima, Yasunori Yamamoto, Atsuko Yamaguchi, Shinobu Okamoto, Shin Kawano, Jin-Dong Kim, Yue Wang, Hongyan Wu, Yoshinobu Kano, Hiromasa Ono, Hidemasa Bono, Simon Kocbek, Jan Aerts, Yukie Akune, Erick Antezana, Kazuharu Arakawa, Bruno Aranda, Joachim Baran, Jerven Bolleman, Raoul JP Bonnal, Pier Buttigieg, Matthew P Campbell, Yi-an Chen, Hirokazu Chiba, Peter JA Cock, K Cohen, Alexandru Constantin, Geraint Duck, Michel Dumontier, Takatomo Fujisawa, Toyofumi Fujiwara, Naohisa Goto, Robert Hoehndorf, Yoshinobu Igarashi, Hidetoshi Itaya, Maori Ito, Wataru Iwasaki, Matúš Kalaš, Takeo Katoda, Taehong Kim, Anna Kokubu, Yusuke Komiyama, Masaaki Kotera, Camille Laibe, Hilmar Lapp, Thomas Lütteke, M Marshall, Takaaki Mori, Hiroshi Mori, Mizuki Morita, Katsuhiko Murakami, Mitsuteru Nakao, Hisashi Narimatsu, Hiroyo Nishide, Yosuke Nishimura, Johan Nystrom-Persson, Soichi Ogishima, Yasunobu Okamura, Shujiro Okuda, Kazuki Oshita, Nicki H Packer, Pjotr Prins, Rene Ranzinger, Philippe Rocca-Serra, Susanna Sansone, Hiromichi Sawaki, Sung-Ho Shin, Andrea Splendiani, Francesco Strozzi, Shu Tadaka, Philip Toukach, Ikuo Uchiyama, Masahito Umezaki, Rutger Vos, Patricia L Whetzel, Issaku Yamada, Chisato Yamasaki, Riu Yamashita, William S York, Christian M Zmasek, Shoko Kawamoto, Toshihisa Takagi. BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains. Journal of Biomedical Semantics 2014, 5 (1) , 5. https://doi.org/10.1186/2041-1480-5-5
- Minoru Kanehisa. Chemical and genomic evolution of enzyme‐catalyzed reaction networks. FEBS Letters 2013, 587 (17) , 2731-2737. https://doi.org/10.1016/j.febslet.2013.06.026
- Minoru Kanehisa. Automated interpretation of metabolic capacity from genome and metagenome sequences. Quantitative Biology 2013, 1 (3) , 192-200. https://doi.org/10.1007/s40484-013-0019-x
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References
ARTICLE SECTIONS
This article references 28 other publications.
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1Bono, H.; Ogata, H.; Goto, S.; Kanehisa, M. Reconstruction of amino acid biosynthesis pathways from the complete genome sequence Genome Res. 1998, 8, 203– 2101https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1cXitlWksrg%253D&md5=fc164a7deefa6b03be0c5512d7229545Reconstruction of amino acid biosynthesis pathways from the complete genome sequenceBono, Hidemasa; Ogata, Hiroyuki; Goto, Susumu; Kanehisa, MinoruGenome Research (1998), 8 (3), 203-210CODEN: GEREFS; ISSN:1088-9051. (Cold Spring Harbor Laboratory Press)The complete genome sequence of an organism contains information that has not been fully utilized in the current prediction methods of gene functions, which are based on piece-by-piece similarity searches of individual genes. A method is presented a method that utilizes a higher level information of mol. pathways to reconstruct a complete functional unit from a set of genes. Specifically, a genome-by-genome comparison is first made for identifying enzyme genes and assigning EC nos., which is followed by the reconstruction of selected portions of the metabolic pathways by use of the reconstructed pathway is an indicator of the correctness of the initial gene function assignment. This feature has become possible because of efforts to computerize the current knowledge of metabolic pathways under the KEGG project. The biosynthesis pathway of all 20 amino acids were completely reconstructed in Escherichia coli, Haemophilus influenzae, and Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as well, although it was necessary to assume wilder substrate specificity for aspartate aminotransferases.
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2Galperin, M. Y.; Koonin, E. V. Functional genomics and enzyme evolution. Homologous and analogous enzymes encoded in microbial genomes Genetica 1999, 106, 159– 170There is no corresponding record for this reference.
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3Dandekar, T.; Schuster, S.; Snel, B.; Huynen, M.; Bork, P. Pathway alignment: application to the comparative analysis of glycolytic enzymes Biochem. J. 1999, 343, 115– 124There is no corresponding record for this reference.
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4Forst, C. V.; Schulten, K. Evolution of metabolisms: a new method for the comparison of metabolic pathways using genomics information J. Comput. Biol. 1999, 6, 343– 3604https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXns1enuro%253D&md5=81eea3db60585f2a55d9f79c09274c4eEvolution of metabolisms: a new method for the comparison of metabolic pathways using genomics informationForst, Christian V.; Schulten, KlausJournal of Computational Biology (1999), 6 (3/4), 343-360CODEN: JCOBEM; ISSN:1066-5277. (Mary Ann Liebert, Inc.)The abundance of information provided by completely sequenced genomes defines a starting point for new insights in the multilevel organization of organisms and their evolution. At the lowest level enzymes and other protein complexes are formed by aggregating multiple polypeptides. At a higher level enzymes group conceptually into metabolic pathways as part of a dynamic information-processing system, and substrates are processed by enzymes yielding other substrates. A method based on a combination of sequence information with graph topol. of the underlying pathway is presented. With this approach pathways of different organisms are related to each other by phylogenetic anal., extending conventional phylogenetic anal. of individual enzymes. The new method is applied to pathways related to electron transfer and to the Krebs citric acid cycle. In addn. to providing a more comprehensive understanding of similarities and differences between organisms, this method indicates different evolutionary rates between substrates and enzymes.
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5Ogata, H.; Fujibuchi, W.; Goto, S.; Kanehisa, M. A heuristic graph comparison algorithm and its application to detect functionally related enzyme clusters Nucleic Acids Res. 2000, 28, 4021– 4028There is no corresponding record for this reference.
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6Tohsato, Y.; Matsuda, H.; Hashimoto, A. A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchy Proc. Int. Conf. Intell. Syst. Mol. Biol. 2000, 8, 376– 3836https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD3M7gt1artQ%253D%253D&md5=af098d7d4bb217e243aceb490a1afd59A multiple alignment algorithm for metabolic pathway analysis using enzyme hierarchyTohsato Y; Matsuda H; Hashimoto AProceedings / ... International Conference on Intelligent Systems for Molecular Biology ; ISMB. International Conference on Intelligent Systems for Molecular Biology (2000), 8 (), 376-83 ISSN:1553-0833.In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Comparative analyses of the metabolic pathways formed by such reactions give important information on their evolution and on pharmacological targets (Dandekar et al. 1999). Each of the enzymes that constitute a pathway is classified according to the EC (Enzyme Commission) numbering system, which consists of four sets of numbers that categorize the type of the chemical reaction catalyzed. In this study, we consider that reaction similarities can be expressed by the similarities between EC numbers of the respective enzymes. Therefore, in order to find a common pattern among pathways, it is desirable to be able to use the functional hierarchy of EC numbers to express the reaction similarities. In this paper, we propose a multiple alignment algorithm utilizing information content that is extended to symbols having a hierarchical structure. The effectiveness of our method is demonstrated by applying the method to pathway analyses of sugar, DNA and amino acid metabolisms.
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7Pinter, R. Y.; Rokhlenko, O.; Yeger-Lotem, E.; Ziv-Ukelson, M. Alignment of metabolic pathways Bioinformatics 2005, 21, 3401– 3408There is no corresponding record for this reference.
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8Wernicke, S.; Rasche, F. Simple and fast alignment of metabolic pathways by exploiting local diversity Bioinformatics 2007, 23, 1978– 1985There is no corresponding record for this reference.
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9Tohsato, Y.; Nishimura, Y. Reaction similarities focusing substructure changes of chemical compounds and metabolic pathway alignments Inf. Media Technol. 2009, 4, 390– 399There is no corresponding record for this reference.
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10Ay, Y.; Kellis, M.; Kahveci, T. SubMAP: aligning metabolic pathways with subnetwork mappings J. Comput. Biol. 2011, 18, 219– 23510https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXjtlSjt7g%253D&md5=f9f9250ab813c22517f669e458a4b0bbSubMAP: aligning metabolic pathways with subnetwork mappingsAy, Ferhat; Kellis, Manolis; Kahveci, TamerJournal of Computational Biology (2011), 18 (3), 219-235CODEN: JCOBEM; ISSN:1557-8666. (Mary Ann Liebert, Inc.)We consider the problem of aligning two metabolic pathways. Unlike traditional approaches, we do not restrict the alignment to one-to-one mappings between the mols. (nodes) of the input pathways (graphs). We follow the observation that, in nature, different organisms can perform the same or similar functions through different sets of reactions and mols. The no. and the topol. of the mols. in these alternative sets often vary from one organism to another. With the motivation that an accurate biol. alignment should be able to reveal these functionally similar mol. sets across different species, we develop an algorithm that first measures the similarities between different nodes using a mixt. of homol. and topol. similarity. We combine the two metrics by employing an eigenvalue formulation. We then search for an alignment between the two input pathways that maximizes a similarity score, evaluated as the sum of the similarities of the mapped subnetworks of size at most a given integer k, and also does not contain any conflicting mappings. Here we prove that this maximization is NP-hard by a redn. from the max. wt. independent set (MWIS) problem. We then convert our problem to an instance of MWIS and use an efficient vertex-selection strategy to ext. the mappings that constitute our alignment. We name our algorithm SubMAP (Subnetwork Mappings in Alingment of Pathways). We evaluate its accuracy and performance on real datasets. Our empirical results demonstrate that SubMAP can identify biol. relevant mappings that are missed by traditional alignment methods. Furthermore, we observe that SubMAP is scalable for metabolic pathways of arbitrary topol., including searching for a query pathway of size 70 against the complete KEGG database of 1,842 pathways.
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11Kanehisa, M.; Goto, S.; Sato, Y.; Furumichi, M.; Tanabe, M. KEGG for integration and interpretation of large-scale molecular data sets Nucleic Acids Res. 2012, 40, D109– D11411https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs12htbrO&md5=d234c2f8945fbec1d3767e11fa96710bKEGG for integration and interpretation of large-scale molecular data setsKanehisa, Minoru; Goto, Susumu; Sato, Yoko; Furumichi, Miho; Tanabe, MaoNucleic Acids Research (2012), 40 (D1), D109-D114CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/ or http://www.kegg.jp/) is a database resource that integrates genomic, chem. and systemic functional information. In particular, gene catalogs from completely sequenced genomes are linked to higher-level systemic functions of the cell, the organism and the ecosystem. Major efforts have been undertaken to manually create a knowledge base for such systemic functions by capturing and organizing exptl. knowledge in computable forms; namely, in the forms of KEGG pathway maps, BRITE functional hierarchies and KEGG modules. Continuous efforts have also been made to develop and improve the cross-species annotation procedure for linking genomes to the mol. networks through the KEGG Orthol. system. Here we report KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets. We also report a variant of the KEGG mapping procedure to extend the knowledge base, where different types of data and knowledge, such as disease genes and drug targets, are integrated as part of the KEGG mol. networks. Finally, we describe recent enhancements to the KEGG content, esp. the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics.
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12Kotera, M.; Okuno, Y.; Hattori, M.; Goto, S.; Kanehisa, M. Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions J. Am. Chem. Soc. 2004, 126, 16487– 1649812https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhtVCisb%252FM&md5=901f1cbf5fc79870f63fcca0a9ff2004Computational Assignment of the EC Numbers for Genomic-Scale Analysis of Enzymatic ReactionsKotera, Masaaki; Okuno, Yasushi; Hattori, Masahiro; Goto, Susumu; Kanehisa, MinoruJournal of the American Chemical Society (2004), 126 (50), 16487-16498CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The EC (Enzyme Commission) nos. represent a hierarchical classification of enzymic reactions, but they are also commonly utilized as identifiers of enzymes or enzyme genes in the anal. of complete genomes. This duality of the EC nos. makes it possible to link the genomic repertoire of enzyme genes to the chem. repertoire of metabolic pathways, the process called metabolic reconstruction. Unfortunately, there are numerous reactions known to be present in various pathways, but they will never get EC nos. because the EC no. assignment requires published articles on full characterization of enzymes. Here we report a computerized method to automatically assign the EC nos. up to the sub-subclasses, i.e., without the fourth serial no. for substrate specificity, given pairs of substrates and products. The method is based on a new classification scheme of enzymic reactions, named the RC (reaction classification) no. Each reaction in the current dataset of the EC nos. is first decompd. into reactant pairs. Each pair is then structurally aligned to identify the reaction center, the matched region, and the difference region. The RC no. represents the conversion patterns of atom types in these three regions. We examd. the correspondence between computationally assigned RC nos. and manually assigned EC nos. by the jackknife cross-validation test and found that the EC sub-subclasses could be assigned with the accuracy of about 90%. Furthermore, we examd. the correlation with genomic information as represented by the KEGG ortholog clusters (OC) and confirmed that the RC nos. are correlated not only with elementary reaction mechanisms but also with protein families.
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13McDonald, A. G.; Boyce, S.; Tipton, K. F. ExplorEnz: the primary source of the IUBMB enzyme list Nucleic Acids Res. 2009, 37, D593– D597There is no corresponding record for this reference.
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14Hattori, M.; Okuno, Y.; Goto, S.; Kanehisa, M. Development of a chemical structure comparison method for integrated analysis of chemical and genomic information in the metabolic pathways J. Am. Chem. Soc. 2003, 125, 11853– 1186514https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXnt1Knuro%253D&md5=6083bca700feacbf75695fdbe8c79521Development of a Chemical Structure Comparison Method for Integrated Analysis of Chemical and Genomic Information in the Metabolic PathwaysHattori, Masahiro; Okuno, Yasushi; Goto, Susumu; Kanehisa, MinoruJournal of the American Chemical Society (2003), 125 (39), 11853-11865CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Cellular functions result from intricate networks of mol. interactions, which involve not only proteins and nucleic acids but also small chem. compds. Here we present an efficient algorithm for comparing two chem. structures of compds., where the chem. structure is treated as a graph consisting of atoms as nodes and covalent bonds as edges. On the basis of the concept of functional groups, 68 atom types (node types) are defined for carbon, nitrogen, oxygen, and other at. species with different environments, which has enabled detection of biochem. meaningful features. Maximal common subgraphs of two graphs can be found by searching for maximal cliques in the assocn. graph, and we have introduced heuristics to accelerate the clique finding and to detect optimal local matches (simply connected common subgraphs). Our procedure was applied to the comparison and clustering of 9383 compds., mostly metabolic compds., in the KEGG/LIGAND database. The largest clusters of similar compds. were related to carbohydrates, and the clusters corresponded well to the categorization of pathways as represented by the KEGG pathway map nos. When each pathway map was examd. in more detail, finer clusters could be identified corresponding to subpathways or pathway modules contg. continuous sets of reaction steps. Furthermore, it was found that the pathway modules identified by similar compd. structures sometimes overlap with the pathway modules identified by genomic contexts, namely, by operon structures of enzyme genes.
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15Jensen, R. A. Enzyme recruitment in evolution of new function Annu. Rev. Microbiol. 1976, 30, 409– 42515https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE28XlvVyitLs%253D&md5=c28c95884851c8d4336cb1359898f148Enzyme recruitment in evolution of new functionJensen, Roy A.Annual Review of Microbiology (1976), 30 (), 409-25CODEN: ARMIAZ; ISSN:0066-4227.A review with 96 refs., emphasizing the prospects for defining evolutionary relations between enzymes that coexist in the same organism but that no longer serve the same function.
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16Horie, A.; Tomita, T.; Saiki, A.; Kono, H.; Taka, H.; Mineki, R.; Fujimura, T.; Nishiyama, C.; Kuzuyama, T.; Nishiyama, M. Discovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilus Nat. Chem. Biol. 2009, 5, 673– 67916https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXoslensLs%253D&md5=e9bfcc9ed50f6a0b7e726a9e71fa2f8dDiscovery of proteinaceous N-modification in lysine biosynthesis of Thermus thermophilusHorie, Akira; Tomita, Takeo; Saiki, Asako; Kono, Hidetoshi; Taka, Hikari; Mineki, Reiko; Fujimura, Tsutomu; Nishiyama, Chiharu; Kuzuyama, Tomohisa; Nishiyama, MakotoNature Chemical Biology (2009), 5 (9), 673-679CODEN: NCBABT; ISSN:1552-4450. (Nature Publishing Group)Although the latter portion of lysine biosynthesis, the conversion of α-aminoadipate (AAA) to lysine, in Thermus thermophilus is similar to the latter portion of arginine biosynthesis, enzymes homologous to ArgA and ArgJ are absent from the lysine pathway. Because ArgA and ArgJ are known to modify the amino group of glutamate to avoid intramol. cyclization of intermediates, their absence suggests that the pathway includes an alternative N-modification system. We reconstituted the conversion of AAA to lysine and found that the amino group of AAA is modified by attachment to the γ-carboxyl group of the C-terminal Glu54 of a small protein, LysW; that the side chain of AAA is converted to the lysyl side chain while still attached to LysW; and that lysine is subsequently liberated from the LysW-lysine fusion. The fact that biosynthetic enzymes recognize the acidic globular domain of LysW indicates that LysW acts as a carrier protein or protein scaffold for the biosynthetic enzymes. This study thus reveals the previously unknown function of a small protein in primary metab.
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17Maeder, D. L.; Weiss, R. B.; Dunn, D. M.; Cherry, J. L.; González, J. M.; DiRuggiero, J.; Robb, F. T. Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P. horikoshii inferred from complete genomic sequences Genetics 1999, 152, 1299– 1305There is no corresponding record for this reference.
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18Pelletier, D. A.; Harwood, C. S. 2-Hydroxycyclohexanecarboxyl coenzyme A dehydrogenase, an enzyme characteristic of the anaerobic benzoate degradation pathway used by Rhodopseudomonas palustris J. Bacteriol. 2000, 182, 2753– 276018https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXivFKqs7s%253D&md5=b1c35611674df5eaac568d4f53dc340b2-Hydroxycyclohexanecarboxyl coenzyme A dehydrogenase, an enzyme characteristic of the anaerobic benzoate degradation pathway used by Rhodopseudomonas palustrisPelletier, Dale A.; Harwood, Caroline S.Journal of Bacteriology (2000), 182 (10), 2753-2760CODEN: JOBAAY; ISSN:0021-9193. (American Society for Microbiology)A gene, badH, whose predicted product is a member of the short-chain dehydrogenase/reductase family of enzymes, was recently discovered during studies of anaerobic benzoate degrdn. by the photoheterotrophic bacterium Rhodopseudomonas palustris. Purified histidine-tagged BadH protein catalyzed the oxidn. of 2-hydroxycyclohexanecarboxyl CoA (2-hydroxychc-CoA) to 2-ketocyclohexanecarboxyl-CoA. These compds. are proposed intermediates of a series of three reactions that are shared by the pathways of cyclohexanecarboxylate and benzoate degrdn. used by R. palustris. The 2-hydroxychc-CoA dehydrogenase activity encoded by badH was dependent on the presence of NAD+; no activity was detected with NADP+ as a cofactor. The dehydrogenase activity was not sensitive to oxygen. The enzyme has apparent Km values of 10 and 200 μM for 2-hydroxychc-CoA and NAD+, resp. Western blot anal. with antisera raised against purified His-BadH identified a 27-kDa protein that was present in benzoate- and cyclohexanecarboxylate-grown but not in succinate-grown R. palustris cell exts. The active form of the enzyme is a homotetramer. BadH was detd. to be the first gene in an operon, termed the cyclohexanecarboxylate degrdn. operon, contg. genes required for both benzoate and cyclohexanecarboxylate degrdn. A nonpolar R. palustris badH mutant was unable to grow on benzoate or cyclohexanecarboxylate but had wild-type growth rates on succinate. Cells blocked in expression of the entire cyclohexanecarboxylate degrdn. operon excreted cyclohex-1-ene-1-carboxylate into the growth medium when given benzoate. This confirms that cyclohex-1-ene-1-carboxyl-CoA is an intermediate of anaerobic benzoate degrdn. by R. palustris. This compd. had previously been shown not to be formed by Thauera aromatica, a denitrifying bacterium that degrades benzoate by a pathway that is slightly different from the R. palustris pathway. 2-Hydroxychc-CoA dehydrogenase does not participate in anaerobic benzoate degrdn. by T. aromatica and thus may serve as a useful indicator of an R. palustris-type benzoate degrdn. pathway.
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19Harwood, C. S.; Parales, R. E. The beta-ketoadipate pathway and the biology of self-identity Annu. Rev. Microbiol. 1996, 50, 553– 59019https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XmtFGhtro%253D&md5=69dfa001f3f6c320d33b0c788a1e0aa1The β-ketoadipate pathway and the biology of self-identityHarwood, Caroline S.; Parales, Rebecca E.Annual Review of Microbiology (1996), 50 (), 553-590CODEN: ARMIAZ; ISSN:0066-4227. (Annual Reviews)A review with 163 refs. The β-ketoadipate pathway is a chromosomally encoded convergent pathway for arom. compd. degrdn. that is widely distributed in soil bacteria and fungi. One branch converts protocatechuate, derived from phenolic compds. including p-cresol, 4-hydroxybenzoate and numerous lignin monomers, to β-ketoadipate. The other branch converts catechol, generated from various arom. hydrocarbons, amino aroms., and lignin monomers, also to β-ketoadipate. Two addnl. steps accomplish the conversion of β-ketoadipate to tricarboxylic acid cycle intermediates. Enzyme studies and amino acid sequence data indicate that the pathway is highly conserved in diverse bacteria, including Pseudomonas putida, Acinetobacter calcoaceticus, Agrobacterium tumefaciens, Rhodococcus erythropolis, and many others. The catechol branch of the β-ketoadipate pathway appears to be the evolutionary precursor for portions of the plasmid-borne ortho-pathways for chlorocatechol degrdn. However, accumulating evidence points to an independent and convergent evolutionary origin for the eukaryotic β-ketoadipate pathway. In the face of enzyme conservation, the β-ketoadipate pathway exhibits many permutations in different bacterial groups with respect to enzyme distribution (isoenzymes, points of branch convergence), regulation (inducing metabolites, regulatory proteins), and gene organization. Diversity is also evident in the behavioral responses of different bacteria to β-ketoadipate pathway-assocd. arom. compds. The presence and versatility of transport systems encoded by β-ketoadipate pathway regulons is just beginning to be explored in various microbial groups. It appears that in the course of evolution, natural selection has caused the β-ketoadipate pathway to assume a characteristic set of features or identity in different bacteria. Presumably such identities have been shaped to optimally serve the diverse lifestyles of bacteria.
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20Rabus, R.; Kube, M.; Heider, J.; Beck, A.; Heitmann, K.; Widdel, F.; Reinhardt, R. The genome sequence of an anaerobic aromatic-degrading denitrifying bacterium, strain EbN1 Arch. Microbiol. 2005, 183, 27– 36There is no corresponding record for this reference.
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21Lee, S. H.; Jin, H. M.; Lee, H. J.; Kim, J. M.; Jeon, C. O. Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59 J. Bacteriol. 2012, 194, 54421https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmsFWmtQ%253D%253D&md5=2f3354e3bf9b91c99a7ff36820c18801Complete genome sequence of the BTEX-degrading bacterium Pseudoxanthomonas spadix BD-a59Lee, Seung Hyeon; Jin, Hyun Mi; Lee, Hyo Jung; Kim, Jeong Myeong; Jeon, Che OkJournal of Bacteriology (2012), 194 (2), 544CODEN: JOBAAY; ISSN:0021-9193. (American Society for Microbiology)Pseudoxanthomonas spadix BD-a59, able to metabolize all six BTEX (benzene, toluene, ethylbenzene, and o-, m-, and p-xylene) compds., was isolated from gasoline-contaminated sediment. This report presents the complete 3.45-Mb genome sequence and annotation of strain BD-a59. These advance the understanding of strain BD-a59's genomic properties and pollutant metabolic versatility. The complete genome sequence (3,452,554 bp, 3150 predicted protein-coding sequences) is deposited in GenBank/EMBL/DDBJ with accession no. CP003093.
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22Papin, J. A.; Reed, J. L.; Palsson, B. O. Hierarchical thinking in network biology: the unbiased modularization of biochemical networks Trends Biochem. Sci. 2004, 29, 641– 647There is no corresponding record for this reference.
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23Ravasz, E.; Somera, A. L.; Mongru, D. A.; Oltvai, Z. N.; Barabási, A. L. Hierarchical organization of modularity in metabolic networks Science 2002, 297, 1551– 1555There is no corresponding record for this reference.
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24Schuster, S.; Pfeiffer, T.; Moldenhauer, F.; Koch, I.; Dandekar, T. Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae Bioinformatics 2002, 18, 351– 361There is no corresponding record for this reference.
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25Yamada, T.; Kanehisa, M.; Goto, S. Extraction of phylogenetic network modules from the metabolic network BMC Bioinf. 2006, 7, 13025https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD28vhsFekug%253D%253D&md5=c8b1ec61a032234c2a5f2d0cb8f159a9Extraction of phylogenetic network modules from the metabolic networkYamada Takuji; Kanehisa Minoru; Goto SusumuBMC bioinformatics (2006), 7 (), 130 ISSN:.BACKGROUND: In bio-systems, genes, proteins and compounds are related to each other, thus forming complex networks. Although each organism has its individual network, some organisms contain common sub-networks based on function. Given a certain sub-network, the distribution of organisms common to it represents the diversity of its function. RESULTS: We extracted such "common" sub-networks, defined as "phylogenetic network modules," using phylogenetic profiles and cluster analysis. The enzymes in the same "phylogenetic network module" have similar phylogenetic profiles and related functions. These modules are shown to be phylogenetic building blocks. Furthermore, the network of the modules illustrated hierarchical feature as well as the network of enzymes involved in the metabolism. CONCLUSION: We conclude that phylogenetic network modules are evolutionary conserved functional units in the metabolic network. We claim that our concept of phylogenetic modules provides a more accurate understanding of the evolution of biological networks.
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26Horowitz, N. H. On the evolution of biochemical synthesis Proc. Natl. Acad. Sci USA 1945, 31, 153– 157There is no corresponding record for this reference.
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27Ycas, M. On earlier states of the biochemical system J. Theor. Biol. 1974, 44, 145– 16027https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2cXhtFOhur4%253D&md5=cfea1aa54c197fed53fa8f37dd1eb672Earlier states of the biochemical systemYcas, MartynasJournal of Theoretical Biology (1974), 44 (1), 145-60CODEN: JTBIAP; ISSN:0022-5193.Similarities between essential enzymes indicate homology and therefore origin from a smaller no. of ancestral genes, but there are also indications that the immediately preceding biochem. system was of about the same complexity as the present one. In order to maintain function with a smaller no. of enzymes, earlier enzymes must have been less specific, catalyzing classes of reactions. Lower specificity also resulted in ambiguous translation, each cistron producing a family of related proteins. Though individual protein mols. need not have been less specific, each family as a whole functioned as a catalyst of lower specificity. The no. of kinds of amino acids incorporated into proteins may have been larger than at present. The evidence supporting this, some of its implications, and the kinds of addnl. data that would be useful in such problems are discussed.
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28Chu, H. Y.; Wegel, E.; Osbourn, A. From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants Plant J. 2011, 66, 66– 7928https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXlsVKnurc%253D&md5=991bd057a438dbea360c325fe69559e4From hormones to secondary metabolism: The emergence of metabolic gene clusters in plantsChu, Hoi Yee; Wegel, Eva; Osbourn, AnnePlant Journal (2011), 66 (1), 66-79CODEN: PLJUED; ISSN:0960-7412. (Wiley-Blackwell)A review. Gene clusters for the synthesis of secondary metabolites are a common feature of microbial genomes. Well known examples include clusters for the synthesis of antibiotics in actinomycetes, and also for the synthesis of antibiotics and toxins in filamentous fungi. Until recently, it was thought that genes for plant metabolic pathways were not clustered, and this is certainly true in many cases; however, five plant secondary metabolic gene clusters have now been discovered, all of them implicated in synthesis of defense compds. An obvious assumption might be that these eukaryotic gene clusters have arisen by horizontal gene transfer from microbes, but there is compelling evidence to indicate that this is not the case. This raises intriguing questions about how widespread such clusters are, what the significance of clustering is, why genes for some metabolic pathways are clustered and those for others are not, and how these clusters form. In answering these questions we may hope to learn more about mechanisms of genome plasticity and adaptive evolution in plants. It is noteworthy that for the five plant secondary metabolic gene clusters reported so far, the enzymes for the first committed steps all appear to have been recruited directly or indirectly from primary metabolic pathways involved in hormone synthesis. This may or may not turn out to be a common feature of plant secondary metabolic gene clusters as new clusters emerge.
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Supporting Information
Supporting Information
ARTICLE SECTIONS
KEGG atom types, RDM patterns, fingerprint representation, and similarity scoring of RC entries (Methods); tricarboxylic acid pathway (Figure S1); glucosinolate biosynthesis pathway (Figure S2); carboxyl to amino conversion (Figure S3); fatty acid biosynthesis (Figure S4); beta oxidation (Figure S5); methyl to carboxyl conversion on aromatic ring (Figure S6); amino to carboxyl conversion (Figure S7); nucleotide sugar biosynthesis (Figure S8); phenylpropanoid biosynthesis (Figure S9); and classification of monooxygenases (Figure S10). This information is available free of charge via the Internet at http://pubs.acs.org.
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