Enantioselective Synthesis of Lactic Acid From CO 2 Using a Novel Pyruvate Decarboxylase in a Scalable Biocatalytic Cascade

Biocatalytic cascades offer a promising route for CO 2 ‐fixation into valuable chemicals, addressing the urgent need for efficient, sustainable technologies to reduce CO 2 emissions. This paper describes an enzymatic route converting gaseous CO 2 and acetaldehyde into enantiopure lactic acid, widely used in diverse industries. A newly characterized pyruvate decarboxylase from Neoasia chiangmaiensis (NcPDC) enabled acetaldehyde carboxylation to pyruvate. To suppress the competing carboligation to acetoin, acetaldehyde was reversibly trapped with Tris. Pyruvate was reduced to lactate by lactate dehydrogenase, coupled with glucose dehydrogenase for NADH regeneration via D‐glucose oxidation to D‐gluconic acid. Up to 65% lactate yield was achieved. Repeated acetaldehyde dosing resulted in a 27 mM titer, representing a >100‐fold improvement over previous reports. At 0.5 L scale, using a gas mixture mimicking industrial‐grade CO 2 , we obtained 21 mM D‐(–)‐lactic acid, 42% yield and >98% e.e. , demonstrating scalability and robustness. Finally, replacing the D‐(–)‐selective lactate dehydrogenase with an L‐(+)‐selective variant at small scale enabled production of L‐(+)‐lactic acid at 41% yield and >93% e.e , allowing switchable access to either enantiomer. A volumetric productivity of 1.1 × 10 −2 g L −1 h −1 ranks among the most efficient minimal enzymatic routes developed to date for CO 2 ‐to‐lactate conversion.