Metabolic engineering of Escherichia coli for the production of (R)-α-lipoic acid.

Objective: To increase the production of (R)-α-lipoic acid directly from octanoic acid using engineered Escherichia coli with the regeneration of S-adenosylmethionine.

Results: The biosynthesis of (R)-α-lipoic acid (LA) in E. coli BL21(DE3) is improved by co-expression of lipoate-protein ligase A (LplA) from E. coli MG1655 and lipoate synthase (LipA) from Vibrio vulnificus. The engineered strain produces 20.99 µg l of LA in shake flask cultures. The titers of LA are increased to 169.28 µg l after the optimization of the medium components and fermentation conditions. We find that the [4Fe-4S] cluster is important for the activity of LipA and co-expression of iscSUA promotes the regeneration of the [4Fe-4S] cluster and leads to the highest LA titer of 589.30 µg l.

Conclusion: The method described here can be widely applied for the biosynthesis of (R)-α-lipoic acid and other metabolites.