231_2_revised_manuscript_marked_up_8142_plnszw.pdf (663.88 kB)

Synergistic substrate cofeeding stimulates reductive metabolism

Download (663.88 kB)
journal contribution
posted on 22.05.2020, 13:15 by Junyoung O Park, Nian Liu, Kara M Holinski, David F Emerson, Kangjian Qiao, Benjamin M Woolston, Jingyang Xu, Zbigniew Lazar, Ahsan Islam, Charles Vidoudez, Peter R Girguis, Gregory Stephanopoulos
Advanced 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 Metabolism

Volume

1

Issue

6

Pages

643 - 651

Publisher

Springer Nature

Version

AM (Accepted Manuscript)

Rights holder

© Springer Nature

Publisher 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

13/05/2019

Publication date

2019-06-14

Copyright date

2019

eISSN

2522-5812

Language

en

Depositor

Dr Ahsan Islam. Deposit date: 22 May 2020

Exports

Logo branding

Categories

Exports