Rapid preparation of mycobacterium N-glycolyl Lipid I and Lipid II derivatives: a biocatalytic approach.

Breaking down barriers: A rapid, inexpensive preparation of the structurally complex mycobacterial N-glycolyl Lipid I, Lipid II, and their analogues from a range of different synthetic N-glycolyl and N-glycinyl Park's nucleotides is described (see scheme). The biotransformations were catalyzed by a readily available biocatalyst obtained from a bacterial cell-free membrane fraction. The unnatural N-glycinyl Lipid II was found to be a substrate of Mycobacterium tuberculosis (Mtb) transglycosylase, PonA, and N-glycolyl Lipid I was a weak inhibitor against PonA.