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Acetyl-CoA Synthesis Through a Bicyclic Carbon-Fixing Pathway in Gas-Fermenting Bacteria

Journal Article · · Nature Synthesis
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Gas-fermenting acetogens can upgrade one-carbon (C1) compounds (such as CO2 and CO) to the two-carbon (C2) metabolite acetyl coenzyme A (CoA) and convert sugar feedstocks to acetyl-CoA with minimal CO2 emissions. Fulfilling the biosynthetic potential of these microbes requires overcoming challenges in pathway engineering. Here we design a synthetic acetyl-CoA bi-cycle-in addition to the natural carbon-fixing pathways-for C2 metabolite synthesis. This pathway produces an acetyl-CoA by fixation of two CO2 equivalents via three functional modules acting in sequence: carbon fixation, gluconeogenesis and non-oxidative glycolysis. The pathway was examined by in silico thermodynamic and kinetic analyses. The prototypic pathway was implemented in a syngas-fermenting organism, Clostridium ljungdahlii DSM 13528, by expressing a heterologous phosphoketolase that can work with other native enzymes in the host acetogen. The carbon conversion pathway is possible under various growth conditions and is independent of the Wood-Ljungdahl pathway for the valorization of H2 and CO2. This study reports the improvement of carbon conversion using a reductive acetyl-CoA bi-cycle and the potential impact of redox homoeostasis in the acetogenic host for industrial applications of gas fermentation.

Research Organization:
National Renewable Energy Laboratory (NREL), Golden, CO (United States)
Sponsoring Organization:
USDOE National Renewable Energy Laboratory (NREL), Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Energy Efficiency and Renewable Energy (EERE), Transportation Office. Bioenergy Technologies Office
DOE Contract Number:
AC36-08GO28308
OSTI ID:
2477747
Report Number(s):
NREL/JA-2700-92088; MainId:93866; UUID:8b80765f-2844-46e7-9a92-06bb2a91d876; MainAdminId:74274
Journal Information:
Nature Synthesis, Journal Name: Nature Synthesis Journal Issue: 8 Vol. 1
Country of Publication:
United States
Language:
English

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Related Subjects

Acetyl-CoA
BIOMASS FUELS,INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
carbon conversion pathways
gas-fermenting bacteria
redox homoeostasis