ArticleProceedings of the National Academy of Sciences of the United States of America2012
Inhibitory cross-talk upon introduction of a new metabolic pathway into an existing metabolic network.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 82 citations in OpenAlex.
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- The genetic landscape of a metabolic interaction.Nature communications · 2024Article
- Pyridoxal 5'-phosphate synthesis and salvage in Bacteria and Archaea: predicting pathway variant distributions and holes.Microbial genomics · 2023Article
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- Pyruvate Production by Escherichia coli by Use of Pyruvate Dehydrogenase Variants.Applied and environmental microbiology · 2021Article
- Analysis of metabolic network disruption in engineered microbial hosts due to enzyme promiscuity.Metabolic engineering communications · 2021Article
- Underground metabolism facilitates the evolution of novel pathways for vitamin B6 biosynthesis.Applied microbiology and biotechnology · 2021Review
- Imbalance in Carbon and Nitrogen Metabolism in Comamonas testosteroni R2 Is Caused by Negative Feedback and Rescued by L-arginine.Microbes and environments · 2021Article
- The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease.Frontiers in immunology · 2020Review
- Horizontal transfer of a pathway for coumarate catabolism unexpectedly inhibits purine nucleotide biosynthesis.Molecular microbiology · 2019Article
- Reactive Enamines and Imines In Vivo: Lessons from the RidA Paradigm.Trends in biochemical sciences · 2019Review
- Conserved Pyridoxal 5'-Phosphate-Binding Protein YggS Impacts Amino Acid Metabolism through Pyridoxine 5'-Phosphate inApplied and environmental microbiology · 2019Article
- A Survey of Pyridoxal 5'-Phosphate-Dependent Proteins in the Gram-Positive Model BacteriumFrontiers in molecular biosciences · 2019Review
- Identification of parallel and divergent optimization solutions for homologous metabolic enzymes.Metabolic engineering communications · 2018Article
- Perturbation of the metabolic network in Salmonella enterica reveals cross-talk between coenzyme A and thiamine pathways.PloS one · 2018Article
- Predicting novel substrates for enzymes with minimal experimental effort with active learning.Metabolic engineering · 2017Article
- The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization.Nature communications · 2017Article
- Structural and functional innovations in the real-time evolution of new (βα)Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Evolution or engineering of novel metabolic pathways can endow microbes with new abilities to degrade anthropogenic pollutants or synthesize valuable chemicals. Most studies of the evolution of new pathways have focused on the origins and quality of function of the enzymes involved. However, there is an additional layer of complexity that has received less attention. Introduction of a novel pathway into an existing metabolic network can result in inhibitory cross-talk due to adventitious interactions between metabolites and macromolecules that have not previously encountered one another. Here, we report a thorough examination of inhibitory cross-talk between a novel metabolic pathway for synthesis of pyridoxal 5'-phosphate and the existing metabolic network of Escherichia coli. We demonstrate multiple problematic interactions, including (i) interference by metabolites in the novel pathway with metabolic processes in the existing network, (ii) interference by metabolites in the existing network with the function of the novel pathway, and (iii) diversion of metabolites from the novel pathway by promiscuous activities of enzymes in the existing metabolic network. Identification of the mechanisms of inhibitory cross-talk can reveal the types of adaptations that must occur to enhance the performance of a novel metabolic pathway as well as the fitness of the microbial host. These findings have important implications for evolutionary studies of the emergence of novel pathways in nature as well as genetic engineering of microbes for "green" manufacturing processes.
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