A cryptic lactate cycle in CO fermentation by Clostridium ljungdahlii.

Lactate metabolism in Clostridium ljungdahlii during CO fermentation is linked to an active lactate cycle, with the unlabeled lactate fraction rising from 1.0% (day 2) to 5.0% (day 6).

• Why it matters: Energy constraints and poorly understood pathways limit acetogen cell-factory efficiency, and the physiological basis of autotrophic CO fermentation in Clostridium ljungdahlii remains incompletely defined.
• What they did: The study combined growth/product profiling, 13C-labeling, gene knockouts, and transcriptomics to track lactate production and oxidation and identify lactate dehydrogenases LdhA and the Ldh/EtfAB_1 complex.
• The result: Disrupting the lactate cycle, especially in the Ldh/EtfAB_1 mutant, improved energy metabolism and increased lactate ~10-fold while shifting the acetate/ethanol ratio from 3.7:1 to 2.1:1, with ldhA overexpression raising lactate to ~2.5 mM.