Disruption of an aromatase/cyclase from the oxytetracycline gene cluster of Streptomyces rimosus results in production of novel polyketides with shorter chain lengths

Oxytetracycline is a polyketide antibiotic made by Streptomyces rimosus. Fr om DNA sequencing, the gene product of otcD1 is deduced to function as a bi functional cyclase/aromatase involved in ring closure of the polyketide bac kbone. Although otcD1 is contiguous with the ketoreductase gene, they are l ocated an unusually large distance from the genes encoding the "minimal pol yketide synthase" of the oxytetracycline gene cluster, A recombinant, disru pted in the genomic copy of otcD1, made four novel polyketides, all of shor ter chain length (by up to 10 carbons) than oxytetracycline, All four novel structures contained the unusual carboxamido group, typical of oxytetracyc line, This implies that the carboxamido group is present at the start of bi osynthesis of oxytetracycline, a topic that has been debated in the literat ure, Loss of the cyclase protein has a profound influence on the length of polyketide chain assembled, implying that OtcD1 plays a greater role in the overall integrity of the quaternary structure of the polyketide complex th an hitherto imagined.