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

ChemBioChem
2016.0

Abstract

<jats:title>Abstract</jats:title><jats:p><jats:italic>Streptomyces</jats:italic> 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 <jats:italic>Streptomyces</jats:italic> 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‐((2<jats:italic>E</jats:italic>,4<jats:italic>E</jats:italic>,6<jats:italic>E</jats:italic>,8<jats:italic>E</jats:italic>)‐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.

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