Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens

Cell Systems
Kaspar ValgepeaEsteban Marcellin

Abstract

Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1. This regulatory mechanism eventually leads to depletion of the intracellular acetyl-CoA pool and collapse of metabolism. We accurately predict growth phenotypes using a genome-scale metabolic model. Modeling revealed that the methylene-THF reductase reaction was ferredoxin reducing. This work provides a reference dataset to advance the understanding and engineering of arguably the first carbon fixation pathway on Earth.

Citations

Sep 27, 2018·FEMS Microbiology Letters·Ilyas KabimoldayevDonghyuk Kim
Sep 30, 2018·Biotechnology and Bioengineering·David F EmersonGregory Stephanopoulos
Mar 7, 2018·Biotechnology for Biofuels·Kaspar ValgepeaEsteban Marcellin
Mar 8, 2019·PLoS Computational Biology·Joanne K LiuKarsten Zengler
May 31, 2020·Proceedings of the National Academy of Sciences of the United States of America·Vishnuvardhan MahamkaliEsteban Marcellin
May 18, 2020·Applied and Environmental Microbiology·Zi-Yong LiuFu-Li Li
Sep 8, 2020·Journal of Industrial Microbiology & Biotechnology·Charlotte Anne VeesStefan Pflügl
Apr 19, 2018·Biochemical Society Transactions·Rupert O J NormanCharlie Hodgman
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Renato de Souza Pinto LemgruberEsteban Marcellin
Apr 16, 2020·Frontiers in Bioengineering and Biotechnology·James K HeffernanEsteban Marcellin
Jun 17, 2020·Nature Chemical Biology·Ashty S KarimMichael C Jewett
Jul 13, 2018·Genes·Briardo LlorenteHugh D Goold
Oct 21, 2020·International Journal of Molecular Sciences·Sangrak JinByung-Kwan Cho
Jul 19, 2019·Metabolic Engineering·Sebastian GrenzBastian Blombach
Apr 22, 2020·Current Opinion in Biotechnology·Michael Köpke, Séan D Simpson
Feb 18, 2021·FEMS Microbiology Reviews·Barbara BourgadeM Ahsanul Islam
Jun 16, 2018·Metabolic Engineering·Benjamin M WoolstonGregory Stephanopoulos
Mar 23, 2021·Frontiers in Bioengineering and Biotechnology·Maria HermannRalf Takors
May 20, 2021·Journal of Applied Microbiology·Xiangan Li, Michael A Henson
Nov 30, 2021·Microbial Biotechnology·Jamin C WoodBernardino Virdis

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