Identification of AstG1, A LAL family regulator that positively controls ansatrienins production in Streptomyces sp. XZQH13.

ABSTRACT

Ansamycins is a group of type I polyketides characterized by the unique starter unit 3-amino-5-hydroxybenzoic acid. This family of secondary metabolites shows diverse biological activities, well-known members of which include rifamycin, geldanamycin, and maytansine. Previously, we isolated an AHBA synthase gene-positive strain Streptomyces sp. XZQH13 containing a "silent" ansamycin biosynthetic gene cluster ast. The constitutive expression of the Large-ATP-binding regulators of the LuxR family regulator gene astG1 located within the cluster triggered the expression of the biosynthetic genes. Reverse transcription-PCR experiments showed that the expression of the key biosynthetic genes, astB4, astD1, and astF1, was induced in the astG1 overexpression mutant compared to the wild type. This led to the isolation of two known ansatrienins, hydroxymycotrienin A (1) and thiazinotrienomycin G (2), which were identified by analysis of the mass spectral and NMR spectral data, from the mutant. These observations suggest that astG1 is probably a pathway-specific positive regulator for the biosynthesis of ansatrienin.