Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.

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 cellula...

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Main Authors: Hsin-Hung Chou, Christopher J Marx, Uwe Sauer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005007&type=printable
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author Hsin-Hung Chou
Christopher J Marx
Uwe Sauer
author_facet Hsin-Hung Chou
Christopher J Marx
Uwe Sauer
author_sort Hsin-Hung Chou
collection DOAJ
description 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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spelling doaj-art-d26881f5c4a4466c8b3ebbcbb772d04f2025-08-20T02:15:13ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-01-01112e100500710.1371/journal.pgen.1005007Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.Hsin-Hung ChouChristopher J MarxUwe SauerMetabolic 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005007&type=printable
spellingShingle Hsin-Hung Chou
Christopher J Marx
Uwe Sauer
Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
PLoS Genetics
title Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
title_full Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
title_fullStr Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
title_full_unstemmed Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
title_short Transhydrogenase promotes the robustness and evolvability of E. coli deficient in NADPH production.
title_sort transhydrogenase promotes the robustness and evolvability of e coli deficient in nadph production
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1005007&type=printable
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AT uwesauer transhydrogenasepromotestherobustnessandevolvabilityofecolideficientinnadphproduction