Investigating Biosynthetic Steps of an Angucycline Antifungal
Abstract
From the bacterium Streptomyces sp. SCC-2136 (ATCC 55186), two angucycline natural products are produced, designated Sch 47554 and Sch 47555. These compounds are produced through a type II polyketide biosynthetic pathway. The early biosynthetic steps to these molecules were confirmed. These include the minimal polyketide synthase (PKS), the C-9 ketoreductase, the first-ring aromatase, the subsequent ring cyclase, and two oxy-genases. Also confirmed were the biosynthetic genes responsible for production of the first amicetose moiety, as well as the glycosyltransferase that creates a C-glycosidic bond between the angucyclic scaffold and the amicetose moiety. In confirming these pathways, two new natural products were produced: GG31, an amitosylated rabelomycin, and GG53, rabelomycin hydroxylated at C-12b. Future work will be to understand the late biosynthetic steps and generate new angucyclines through combinatorial biosynthesis.