New tricyclic geldanamycin analogues from an engineered strain of Streptomyces hygroscopicus JCM4427

Abstract Two tricyclic geldanamycin analogues, DHQ5 ( 1 ) and DHQ6 ( 2 ), were produced by a combinatorial mutant (AC15) contained a site-directed mutagenesis on the geldanamycin polyketide synthase (PKS) gene with inactivation of the post-PKS tailoring genes ( gel7 ) of Streptomyces hygroscopicus JCM4427. The structural diversity of tricyclic geldanamycin analogues is due to the formation of unusual additional rings, which are formed by alkylation of the C-21 position by C-12 in DHQ5 ( 1 ) and by electrophilic addition of the C-15 hydroxyl group to the double bond (C-8–C-9), which leads to the migration of the double bond (to C-7–C-8) and the elimination of a carbamoyloxy group in DHQ6 ( 2 ).