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

Elad Herz, Niv Antonovsky, Yinon Bar-On, Dan Davidi, Shmuel Gleizer, Noam Prywes, Lianet Noda-Garcia, Keren Lyn Frisch, Yehudit Zohar, David G. Wernick, Alon Savidor, Uri Barenholz and Ron Milo ()
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Elad Herz: Weizmann Institute of Science
Niv Antonovsky: Weizmann Institute of Science
Yinon Bar-On: Weizmann Institute of Science
Dan Davidi: Weizmann Institute of Science
Shmuel Gleizer: Weizmann Institute of Science
Noam Prywes: Weizmann Institute of Science
Lianet Noda-Garcia: Weizmann Institute of Science
Keren Lyn Frisch: Weizmann Institute of Science
Yehudit Zohar: Weizmann Institute of Science
David G. Wernick: Weizmann Institute of Science
Alon Savidor: Weizmann Institute of Science
Uri Barenholz: Weizmann Institute of Science
Ron Milo: Weizmann Institute of Science

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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 CO2 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 CO2 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.

Date: 2017
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DOI: 10.1038/s41467-017-01835-3

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