Production of a Novel Amide-Containing Polyene by Activating a Cryptic Biosynthetic Gene Cluster in Streptomyces sp. MSC090213JE08.

Streptomyces sp. MSC090213JE08 seems to have more than 20 cryptic biosynthetic gene clusters for secondary metabolites. We aimed to activate some of them by forced production of Streptomyces antibiotic regulatory protein (SARP) family transcriptional activators. We constructed seven recombinant strains, each of which contained a SARP gene under the control of a constitutive promoter, and subjected them to comparative metabolic profiling analysis. Four of the seven strains produced nine metabolites that were hardly detected in the control strains. We isolated a new metabolite (named ishigamide) from the SARP-7-expressing strain and determined its structure as 3-((2E,4E,6E,8E)-13-hydroxytetradeca-2,4,6,8-tetraenamido)propanoic acid. Genome scanning and gene disruption studies identified the ishigamide biosynthetic gene cluster adjacent to the SARP-7 gene. We think that a new subfamily of type II polyketide synthase is involved in the biosynthesis of the polyene structure of ishigamide.