Interactive Regulation of Formate Dehydrogenase during CO 2 Fixation in Gas-Fermenting Bacteria

Microbial CO 2 fixation and conversion constitute a potential solution to both utilization of greenhouse gas or industrial waste gases and sustainable production of bulk chemicals and fuels. Autotrophic gas-fermenting bacteria play central roles in this bioprocess. This study provides new insights regarding the metabolic regulatory mechanisms underlying CO 2 reduction in Clostridium ljungdahlii , a representative gas-fermenting bacterium. A critical formate dehydrogenase (FDH1) responsible for fixing CO 2 and a dominant reversible lysine acetylation system, At2/Dat1, were identified. Furthermore, FDH1 was found to be interactively regulated by both the At2/Dat1 system and the global transcriptional factor CcpA, and the two regulatory systems are mutually restricted. Reconstruction of this multilevel metabolic regulatory module led to improved CO 2 metabolism by C. ljungdahlii . These findings not only substantively expand our understanding but also provide a potentially useful metabolic engineering strategy for microbial carbon fixation.