The genetic basis for the adaptation of E. coli to sugar synthesis from CO2

Understanding the evolution of a new metabolic capability in full mechanistic detail is challenging, as causative mutations may be masked by non-essential "hitchhiking" mutations accumulated during the evolutionary trajectory. We have previously used adaptive laboratory evolution of a rati...

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Published in:Nature communications 2017-11, Vol.8 (1), p.1-10, Article 1705
Main Authors: Herz, Elad, Antonovsky, Niv, Bar-On, Yinon, Davidi, Dan, Gleizer, Shmuel, Prywes, Noam, Noda-Garcia, Lianet, Lyn Frisch, Keren, Zohar, Yehudit, Wernick, David G., Savidor, Alon, Barenholz, Uri, Milo, Ron
Format: Article
Language:English
Subjects:
631/181/2475
631/326/41/2173
631/553/318
Biological evolution
Carbon dioxide
Carbon fixation
Catalysis
E coli
Efflux
Enzymes
Evolution
Humanities and Social Sciences
Intermediates
Metabolism
multidisciplinary
Mutation
Regulators
Science
Science (multidisciplinary)
Sugar
Synthesis
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Summary:Understanding the evolution of a new metabolic capability in full mechanistic detail is challenging, as causative mutations may be masked by non-essential "hitchhiking" mutations accumulated during the evolutionary trajectory. We have previously used adaptive laboratory evolution of a rationally engineered ancestor to generate an Escherichia coli strain able to utilize CO 2 fixation for sugar synthesis. Here, we reveal the genetic basis underlying this metabolic transition. Five mutations are sufficient to enable robust growth when a non-native Calvin–Benson–Bassham cycle provides all the sugar-derived metabolic building blocks. These mutations are found either in enzymes that affect the efflux of intermediates from the autocatalytic CO 2 fixation cycle toward biomass ( prs , serA , and pgi ), or in key regulators of carbon metabolism ( crp and ppsR ). Using suppressor analysis, we show that a decrease in catalytic capacity is a common feature of all mutations found in enzymes. These findings highlight the enzymatic constraints that are essential to the metabolic stability of autocatalytic cycles and are relevant to future efforts in constructing non-native carbon fixation pathways. An E. coli strain able to use CO 2 fixation for sugar synthesis was previously generated by experimental evolution of an engineered strain. Here, Herz et al. show that specific mutations in five genes, encoding carbon metabolism enzymes or key regulators, are sufficient to enable robust growth of the strain.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01835-3