ArticleProceedings of the National Academy of Sciences of the United States of America2014
Network-level architecture and the evolutionary potential of underground metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64 citing papers in PubMed.
- Metabolic set theory: a generalized model of microbial interactions.NPJ systems biology and applications · 2026Article
- Systematic discovery of enzyme promiscuity in Escherichia coli using in vitro metabolomics.Communications biology · 2026Article
- Discovery and engineering of bifunctional enzymes for lignocellulose degradation: Metagenomic and computational approaches.Biotechnology reports (Amsterdam, Netherlands) · 2025Review
- Computational approaches to enzymatic reaction assignment: a review of methods, validations, and future directions.Briefings in bioinformatics · 2025Review
- Rewiring Aromatic Compound Consumption: Chromosomal Amplification and Evolution of a Foreign Pathway inACS synthetic biology · 2025Article
- Enzyme promiscuity in the field of synthetic biology applied to white biotechnology: Opportunities and weaknesses.Biodesign research · 2025Review
- Protein-constrained models pinpoints the role of underground metabolism in robustness of metabolic phenotypes.iScience · 2025Article
- Into the metabolic wild: Unveiling hidden pathways of microbial metabolism.Microbial biotechnology · 2024Article
- Measuring Molecular Complexity.ACS central science · 2024Article
- CRISPRi-induced transcriptional regulation of IAH1 gene and its influence on volatile compounds profile in Kluyveromyces marxianus DU3.World journal of microbiology & biotechnology · 2024Article
- Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Architecture of Metabolic Networks Constrains the Evolution of Microbial Resource Hierarchies.Molecular biology and evolution · 2023Article
- Filling gaps in metabolism using hypothetical reactions.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mechanisms of protein evolution.Protein science : a publication of the Protein Society · 2022Review
- Development of a genome-targeting mutator for the adaptive evolution of microbial cells.Nucleic acids research · 2022Article
- Networks and Graphs Discovery in Metabolomics Data Analysis and Interpretation.Frontiers in molecular biosciences · 2022Review
- Approaches for completing metabolic networks through metabolite damage and repair discovery.Current opinion in systems biology · 2021Review
- Cysteine and iron accelerate the formation of ribose-5-phosphate, providing insights into the evolutionary origins of the metabolic network structure.PLoS biology · 2021Article
- Diversity begets diversity during community assembly until ecological limits impose a diversity ceiling.Molecular ecology · 2021Article
- Underground metabolism facilitates the evolution of novel pathways for vitamin B6 biosynthesis.Applied microbiology and biotechnology · 2021Review
4 more citing papers are in PubMed but not listed here.
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13 authors.
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Abstract
A central unresolved issue in evolutionary biology is how metabolic innovations emerge. Low-level enzymatic side activities are frequent and can potentially be recruited for new biochemical functions. However, the role of such underground reactions in adaptation toward novel environments has remained largely unknown and out of reach of computational predictions, not least because these issues demand analyses at the level of the entire metabolic network. Here, we provide a comprehensive computational model of the underground metabolism in Escherichia coli. Most underground reactions are not isolated and 45% of them can be fully wired into the existing network and form novel pathways that produce key precursors for cell growth. This observation allowed us to conduct an integrated genome-wide in silico and experimental survey to characterize the evolutionary potential of E. coli to adapt to hundreds of nutrient conditions. We revealed that underground reactions allow growth in new environments when their activity is increased. We estimate that at least ∼20% of the underground reactions that can be connected to the existing network confer a fitness advantage under specific environments. Moreover, our results demonstrate that the genetic basis of evolutionary adaptations via underground metabolism is computationally predictable. The approach used here has potential for various application areas from bioengineering to medical genetics.
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