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Clostridium ljungdahlii  derives energy by lithotrophic and organotrophic acetogenesis.  C .  ljungdahlii  was grown organotrophically with fructose and also lithotrophically, either with syngas - a gas mixture containing hydrogen (H 2 ), carbon dioxide (CO 2 ), and carbon monoxide (CO), or with H 2  and CO 2 . Gene expression was compared quantitatively by microarrays using RNA extracted from all three conditions. Gene expression with fructose and with H 2 /CO 2  was compared by RNA-Seq. Upregulated genes with both syngas and H 2 /CO 2  (compared to fructose) point to the urea cycle, uptake and degradation of peptides and amino acids, response to sulfur starvation, potentially NADPH-producing pathways involving  (S) -malate and ornithine, quorum sensing, sporulation, and cell wall remodeling, suggesting a global and multicellular response to lithotrophic conditions. With syngas, the upregulated  (R) -lactate dehydrogenase gene represents a route of electron transfer from ferredoxin to NAD. With H 2 /CO 2 , flavodoxin and histidine biosynthesis genes were upregulated. Downregulated genes corresponded to an intracytoplasmic microcompartment for disposal of methylglyoxal, a toxic byproduct of glycolysis, as 1-propanol. Several cytoplasmic and membrane-associated redox-active protein genes were differentially regulated. The transcriptomic profiles of  C .  ljungdahlii  in lithotrophic and organotrophic growth modes indicate large-scale physiological and metabolic differences, observations that may guide biofuel and commodity chemical production with this species.

Transcriptomic profiles of Clostridium ljungdahlii during lithotrophic growth with syngas or H2 and CO2 compared to organotrophic growth with fructose