BioChem - DOS

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

Cell systems

Valgepea, K.; de Souza Pinto Lemgruber, R.; Meaghan, K.; Palfreyman, R.W.; Abdalla, T.; Heijstra, B.D.; Behrendorff, J.B.; Tappel, R.; Kopke, M.; Simpson, S.D.; Nielsen, L.K.; Marcellin, E.

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.

2017

Cell Press

publisher-specific-oa

2405-4712

2405-4720

4

5

pp.505-515.e5

10.1016/j.cels.2017.04.008

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART77886647

http://www.cell.com/article/S2405471217301400/pdf

gas fermentation; syngas fermentation; acetogen metabolism; systems biology; genome-scale model; modeling; RNA sequencing; intracellular metabolomics; Clostridium autoethanogenum