Biosynthesis of nitrogen-containing natural products, C7N aminocyclitols and bis-indoles, from actinomycetes

Abstract

Actinomycetes are a major source of bioactive natural products with important pharmaceutical properties. Understanding the natural enzymatic assembly of complex small molecules is important for rational metabolic pathway design to produce "artificial" natural products in bacterial cells. This review will highlight current research on the biosynthetic mechanisms of two classes of nitrogencontaining natural products, C7N aminocyclitols and bis-indoles. Validamycin A is a member of C7N aminocyclitol natural products from Streptomyces hygroscopicus. Here, two important biosynthetic steps, pseudoglycosyltranferase-catalyzed C-N bond formation, and C7-sugar phosphate cyclase-catalyzed divergent carbasugar formation, will be reviewed. In addition, the bis-indolic natural products indolocarbazole, staurosporine from Streptomyces sp. TPA0274, and rearranged bis-indole violacein from Chromobacterium violaceum are reviewed including the oxidative course of the assembly pathway for the bis-indolic scaffold. The identified biosynthesis mechanisms will be useful to generating new biocatalytic tools and bioactive compounds.