Characterization of the Aminosugar Biosynthetic and Regulatory Genes of Vicenistatin in -Associated SCSIO Mla-L010.

Vicenistatin () is a potent polyketide antitumor antibiotic composed of a 20-membered macrolactam core appended to a unique aminosugar, vicenisamine. In this study, vicenistatin was isolated and its biosynthetic gene cluster identified from -associated SCSIO Mla-L010. A set of five genes, , , , , and , was confirmed to be involved in the biosynthesis of the aminosugar by gene inactivations. VicG was characterized as an -methyltransferase that catalyzes the methylation of the 4'-amino group in the last step of the aminosugar biosynthetic pathway; the -demethyl intermediate 4'--demethylvicenistatin () was isolated from the Δ mutant strain. In addition, was characterized as a positive pathway-specific regulatory gene. Notably, -demethyl compound was found to exert impressive antibacterial activities, with MIC values spanning 0.06-4 μg/mL, against a panel of Gram-positive bacteria including methicillin-resistant , Gram-negative , and mycobacterium and the fungal pathogen . Compound was also found to display reduced cytotoxicities relative to vicenistatin, especially against noncancerous human cell lines.