Monday, August 12, 2013
Pavilion (Sheraton San Diego)
Abstract: Meroterpenoids are natural hybrid compounds of mixed polyketide- terpenoid origin that often exhibit broad antibiotic and anticancer activity. The marine-derived Streptomyces sp. CNH-099 produces two distinct prenylated naphthoquinones, marinone and neomarinone, that harbor distinguishing sesquiterpenoid units attached to similar naphthoquinone core molecules. To understand the molecular logic of their differential assembly, we sequenced the draft genome of Streptomyces sp. CNH-099 and directly cloned the 60-kb marinone biosynthesis (mrn) gene cluster from gDNA by transformation-associated recombination in yeast. The gene cluster unexpectedly harbors three vanadium-dependent haloperoxidases genes that putatively brominate the naphthoquinone core via novel bacterial halogenation biochemistry. To elucidate the divergent biosynthetic pathway of the marinones and the function of the haloperoxidases, we performed a series of in vivo and in vitro experiments. Results from these complementary experiments will be presented.