Origins of specificity and promiscuity in metabolic networks
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How enzymes have evolved to their present form is linked to the question of how pathways emerged and evolved into extant metabolic networks. To investigate this mechanism, we have explored the chemical diversity present in a largely unbiased data set of catalytic reactions processed by modern enzymes across the tree of life. In order to get a quantitative estimate of enzyme chemical diversity, we measure enzyme multispecificity or promiscuity using the reaction molecular signatures. Our main finding is that reactions that are catalyzed by a highly specific enzyme are shared by poorly divergent species, suggesting a later emergence of this function during evolution. In contrast, reactions that are catalyzed by highly promiscuous enzymes are more likely to appear uniformly distributed across species in the tree of life. From a functional point of view, promiscuous enzymes are mainly involved in amino acid and lipid metabolisms, which might be associated with the earliest form of biochemical reactions. In this way, results presented in this paper might assist us with the identification of primeval promiscuous catalytic functions contributing to life's minimal metabolism.
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Environmental or geological changes could have led to innovation of increasingly specific and functional catalysts from the initially diverse and chaotic prebiotic milieu.
“Such environmental or geological changes could also have led to innovation of increasingly specific and functional catalysts from the initially diverse and chaotic prebiotic milieu [91,92].”
From Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry (2020) · cites this paper as [92]
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Multifunctional alkalophilic α-amylase with diverse raw seaweed degrading activities
Gu, X., Fu, L., Pan, A., Gui, Y., Zhang, Q., & Jiang, L. (2021) · AMB Express · doi:10.1186/s13568-021-01300-x · Cited by 7 · see citing works
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Moonlighting Biochemistry of Cysteine Synthase: A Species-specific Global Regulator
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SimCAL: a flexible tool to compute biochemical reaction similarity
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Do lifestyles influence the presence of promiscuous enzymes in bacteria and Archaea metabolism?
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Emergence of a Promiscuous Peroxidase Under Non‐Equilibrium Conditions**
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Developing an enzyme selection tool supporting multiple hosts contextsPreprint
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Self-citationMahato, C., Pal, S., Kuiry, H., & Das, D. (2025) · Nano Letters · doi:10.1021/acs.nanolett.4c06230 · Cited by 3 · see citing works
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EnzFIND: Method to identify enzymes for promiscuous biochemical reactions
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Mining conserved neighborhood patterns in metabolic and genomic contexts
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Metabolomics of epigenetics: A history of the integrome
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Uncovering oomycete metabolism using systems biology
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Self-citationDe novo design and synthesis of biomolecules
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Emergence of a Promiscuous Peroxidase Under Non-Equilibrium ConditionsPreprint
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Building Molecules by a Self‐Replicator That Catalyzes Acyl Hydrazone Formation
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Coenzyme-Mediated Enantioselective Carboligation via Cross-β Amyloid Microphases
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Evolution of the retinoic acid receptor
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- Authors
- Carbonell, P., Lecointre, G., & Faulon, J.-L.
- Affiliations
- Institut de Biologie systémique et synthétique (FR)
- Muséum national d'Histoire naturelle (FR)
- Corresponding author
- Faulon, Jean-Loup
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 286
- Issue
- 51
- Pages
- 43994-44004
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3243566
- OpenAlex
- W2128479500
- Cited by
- 87
- References
- 51
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 8 · 2013: 4 · 2012: 6
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- enzyme promiscuity, enzyme specificity, metabolic networks, enzyme evolution, metabolic pathway evolution, amino acid metabolism, lipid metabolism, origin of life
- MeSH terms
- Animals, Biochemistry, Catalysis, Computers, Enzymes, Phylogeny, Software, Substrate Specificity, Models, Statistical, Protein Structure, Tertiary, Evolution, Molecular, Computational Biology, Lipid Metabolism, Metabolic Networks and Pathways
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