Metabolites: a helping hand for pathway evolution?

https://doi.org/10.1016/S0968-0004(03)00114-2 Get rights and content

Abstract

The evolution of enzymes and pathways is under debate. Recent studies show that recruitment of single enzymes from different pathways could be the driving force for pathway evolution. Other mechanisms of evolution, such as pathway duplication, enzyme specialization, de novo invention of pathways or retro-evolution of pathways, appear to be less abundant. Twenty percent of enzyme superfamilies are quite variable, not only in changing reaction chemistry or metabolite type but in changing both at the same time. These variable superfamilies account for nearly half of all known reactions. The most frequently occurring metabolites provide a helping hand for such changes because they can be accommodated by many enzyme superfamilies. Thus, a picture is emerging in which new pathways are evolving from central metabolites by preference, thereby keeping the overall topology of the metabolic network.

Section snippets

Pathway evolution theories

On the level of pathway evolution, several hypotheses have been proposed (Fig. 1). First, pathways might have evolved spontaneously without adopting existing enzymes (Fig. 1a). For example, different tRNA synthetases seem to have initially evolved independently and then later have become involved in different pathways such as protein translation, tRNA dependent transamidation and non-discriminating acylation [15]. Second, the hypothesis of ‘retro-evolution’ of pathways 16, 17 proposes that the

Enzyme variability: reaction change or metabolite change?

Comparative studies on enzyme variability are often based on the definition of enzyme superfamilies – enzymes of common origin that can be identified by sequence and structural homology. The structural homology of an enzyme is important because the position of the catalytic residues in the structure, and the existence and form of different binding clefts is essential for its function and is therefore better conserved than its sequence. Hence, enzyme structure classification databases such as

Some superfamilies change more metabolites and reactions than others

Nature does not seem to favor one mechanism over the other; whether an enzyme superfamily turns out to be more variable or conservative depends on the specific enzyme superfamily. One explanation for the wide range of variability among enzyme superfamilies might be their differences in sequence divergence. Comparing conservative and variable enzyme superfamilies (Fig. 4), the average sequence identity within superfamilies of enzymes catalyzing reactions of one EC class is 38%. The sequence

Impact of highly represented metabolites

Another factor that is important for the variability in metabolite choice of enzyme superfamilies and hence pathway evolution are highly represented metabolites. In a certain way they provide a hook for new pathways. On a note of caution, most of the current data are based on protein or genome information. Far less comes from direct experimental data on enzyme biochemistry or metabolites. It seems probable that a range of different scenarios might have occurred (and be occurring) during pathway

Concluding remarks

Together, current analysis provides us with new insights into the evolution of enzymes and their pathways. Besides the observed limited variability of many enzyme superfamilies in their reaction chemistry and metabolite choice, certain superfamilies appear to have a broader substrate specificity and reaction variability. This variability provides a powerful ‘toolset’ for pathway evolution. Widespread recruitment of enzymes to new pathways becomes possible and is the most often observed mode of

References (58)

  • N.H. Horowitz

    The evolution of biochemical syntheses – retrospect and prospect

  • L.A. Fothergill-Gilmore et al.

    Evolution of glycolysis

    Prog. Biophys. Mol. Biol.

    (1993)
  • G.A. Petsko

    On the origin of enzymatic species

    Trends Biochem. Sci.

    (1993)
  • P.J. O'Brien et al.

    Catalytic promiscuity and the evolution of new enzymatic activities

    Chem. Biol.

    (1999)
  • M.A. Huynen et al.

    Gene and context: integrative approaches to genome analysis

    Adv. Protein Chem.

    (2000)
  • M. Ycas

    On earlier states of the biochemical system

    J. Theor. Biol.

    (1974)
  • A.C. Martin

    Protein folds and functions

    Structure

    (1998)
  • T. Nara

    Evolutionary implications of the mosaic pyrimidine-biosynthetic pathway in eukaryotes

    Gene

    (2000)
  • A.G. Murzin

    SCOP: a structural classification of proteins database for the investigation of sequences and structures

    J. Mol. Biol.

    (1995)
  • P.C. Babbitt et al.

    Understanding enzyme superfamilies

    Chemistry as the fundamental determinant in the evolution of new catalytic activities. J. Biol. Chem.

    (1997)
  • H. Eklund et al.

    Glycyl radical enzymes: a conservative structural basis for radicals

    Structure Fold. Des.

    (1999)
  • J. Qian

    Protein family and fold occurrence in genomes: power-law behaviour and evolutionary model

    J. Mol. Biol.

    (2001)
  • S.D. Copley

    Evolution of a metabolic pathway for degradation of a toxic xenobiotic: the patchwork approach

    Trends Biochem. Sci.

    (2000)
  • A. Broder

    Graph structure in the web

    Comput. Netw.

    (2000)
  • J.A. Gerlt et al.

    Mechanistically diverse enzyme superfamilies: the importance of chemistry in the evolution of catalysis

    Curr. Opin. Chem. Biol.

    (1998)
  • G. Apic

    An insight into domain combinations

    Bioinformatics

    (2001)
  • M. Hrmova

    Structural basis for broad substrate specificity in higher plant β-d-glucan glucohydrolases

    Plant Cell

    (2002)
  • L.A. Nahum et al.

    Divergence of function in sequence-related groups of Escherichia coli proteins

    Genome Res.

    (2001)
  • J.D. Pollack

    Suspected utility of enzymes with multiple activities in the small genome Mycoplasma species: the replacement of the missing ‘household’ nucleoside diphosphate kinase gene and activity by glycolytic kinases

    OMICS

    (2002)
  • Cited by (115)

    • On the evolution of natural product biosynthesis

      2023, Advances in Microbial Physiology
    • The evolution of metabolism: How to test evolutionary hypotheses at the genomic level

      2020, Computational and Structural Biotechnology Journal
      Citation Excerpt :

      Indeed the energy amphiphile core of this hypothesis is consistent with earlier proposals that life evolved on pyrite [264], although the gradual addition of shells, and in particular the late account for sulphur chemistry, are not consistent in light of the recent scenarios for a core organo-sulphur prebiotic metabolism [84]. Whilst all of the above theories have had their supporters, the patchwork recruitment scenario is arguably the best supported by accumulated evidence (see [226]) and [37] for details; we review additional support for the patchwork model with respect to other theories further below). To provide just a handful of examples here, enzymes with (βα)8-barrel fold structure have been found to catalyze similar reactions across pathways [53].

    • Bioinformatics: An Introductory Textbook

      2023, Bioinformatics: an Introductory Textbook
    View all citing articles on Scopus
    View full text