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Synergistic substrate cofeeding stimulates reductive metabolism
journal contribution
posted on 2020-05-22, 13:15 authored by Junyoung O Park, Nian Liu, Kara M Holinski, David F Emerson, Kangjian Qiao, Benjamin M Woolston, Jingyang Xu, Zbigniew Lazar, Ahsan IslamAhsan Islam, Charles Vidoudez, Peter R Girguis, Gregory StephanopoulosAdvanced bioproduct synthesis via reductive metabolism requires coordinating carbons, ATP and reducing agents, which are generated with varying efficiencies depending on metabolic pathways. Substrate mixtures with direct access to multiple pathways may optimally satisfy these biosynthetic requirements. However, native regulation favouring preferential use precludes cells from co-metabolizing multiple substrates. Here we explore mixed substrate metabolism and tailor pathway usage to synergistically stimulate carbon reduction. By controlled cofeeding of superior ATP and NADPH generators as ‘dopant’ substrates to cells primarily using inferior substrates, we circumvent catabolite repression and drive synergy in two divergent organisms. Glucose doping in Moorella thermoacetica stimulates CO2 reduction (2.3 g gCDW−1 h−1) into acetate by augmenting ATP synthesis via pyruvate kinase. Gluconate doping in Yarrowia lipolytica accelerates acetate-driven lipogenesis (0.046 g gCDW−1 h−1) by obligatory NADPH synthesis through the pentose cycle. Together, synergistic cofeeding produces CO2-derived lipids with 38% energy yield and demonstrates the potential to convert CO2 into advanced bioproducts. This work advances the systems-level control of metabolic networks and CO2 use, the most pressing and difficult reduction challenge.
Funding
U.S. Department of Energy grants DE-AR0000433, DE-SC0008744 and DE-SC0012377.
Mobility Plus Fellowship 1284/MOB/IV/2015/0.
History
School
- Mechanical, Electrical and Manufacturing Engineering
Published in
Nature MetabolismVolume
1Issue
6Pages
643 - 651Publisher
Springer NatureVersion
- AM (Accepted Manuscript)
Rights holder
© Springer NaturePublisher statement
This paper was accepted for publication in the journal Nature Metabolism and the definitive published version is available at https://doi.org/10.1038/s42255-019-0077-0.Acceptance date
2019-05-13Publication date
2019-06-14Copyright date
2019eISSN
2522-5812Publisher version
Language
- en
Depositor
Dr Ahsan Islam. Deposit date: 22 May 2020Usage metrics
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