ArticlePLoS genetics2015
Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Evaluating the effects of synthetic POM cycles and NAD+ kinase expression on fatty alcohol production in Saccharomyces cerevisiae.PloS one · 2025Article
- A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations.Nature communications · 2024Article
- Ligand binding and conformational dynamics of theComputational and structural biotechnology journal · 2022Article
- Central Metabolism and Growth Rate Impacts on Hydrogen and Carbon Isotope Fractionation During Amino Acid Synthesis inFrontiers in microbiology · 2022Article
- Dynamic control over feedback regulatory mechanisms improves NADPH flux and xylitol biosynthesis in engineered E. coli.Metabolic engineering · 2021Article
- Evolutionary Repair Experiments as a Window to the Molecular Diversity of Life.Current biology : CB · 2020Review
- Global fitness landscapes of the Shine-Dalgarno sequence.Genome research · 2020Article
- High-Efficient Production of (Molecules (Basel, Switzerland) · 2020Article
- Transcriptome-guided parsimonious flux analysis improves predictions with metabolic networks in complex environments.PLoS computational biology · 2020Article
- Metabolic perturbations in mutants of glucose transporters and their applications in metabolite production in Escherichia coli.Microbial cell factories · 2019Article
- Equilibrium of the intracellular redox state for improving cell growth and L-lysine yield of Corynebacterium glutamicum by optimal cofactor swapping.Microbial cell factories · 2019Article
- Mutations in sigma 70 transcription factor improves expression of functional eukaryotic membrane proteins in Escherichia coli.Scientific reports · 2019Article
- How adaptive evolution reshapes metabolism to improve fitness: recent advances and future outlook.Current opinion in chemical engineering · 2018Article
- Multiple Optimal Phenotypes Overcome Redox and Glycolytic Intermediate Metabolite Imbalances in Escherichia coli pgi Knockout Evolutions.Applied and environmental microbiology · 2018Article
- Control of primary metabolism by a virulence regulatory network promotes robustness in a plant pathogen.Nature communications · 2018Article
- Dissecting the genetic and metabolic mechanisms of adaptation to the knockout of a major metabolic enzyme inProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Growth Adaptation ofFrontiers in microbiology · 2018Article
- Genomic and Transcriptomic Analysis of Growth-Supporting Dehalogenation of Chlorinated Methanes inFrontiers in microbiology · 2017Article
- Functional Trade-Offs in Promiscuous Enzymes Cannot Be Explained by Intrinsic Mutational Robustness of the Native Activity.PLoS genetics · 2016Article
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
Abstract
Metabolic networks revolve around few metabolites recognized by diverse enzymes and involved in myriad reactions. Though hub metabolites are considered as stepping stones to facilitate the evolutionary expansion of biochemical pathways, changes in their production or consumption often impair cellular physiology through their system-wide connections. How does metabolism endure perturbations brought immediately by pathway modification and restore hub homeostasis in the long run? To address this question we studied laboratory evolution of pathway-engineered Escherichia coli that underproduces the redox cofactor NADPH on glucose. Literature suggests multiple possibilities to restore NADPH homeostasis. Surprisingly, genetic dissection of isolates from our twelve evolved populations revealed merely two solutions: (1) modulating the expression of membrane-bound transhydrogenase (mTH) in every population; (2) simultaneously consuming glucose with acetate, an unfavored byproduct normally excreted during glucose catabolism, in two subpopulations. Notably, mTH displays broad phylogenetic distribution and has also played a predominant role in laboratory evolution of Methylobacterium extorquens deficient in NADPH production. Convergent evolution of two phylogenetically and metabolically distinct species suggests mTH as a conserved buffering mechanism that promotes the robustness and evolvability of metabolism. Moreover, adaptive diversification via evolving dual substrate consumption highlights the flexibility of physiological systems to exploit ecological opportunities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.