Genetic architecture of the polyketide synthases for methymycin and pikromycin series macrolides

The methymycin and pikromycin series of antibiotics are structurally relate d macrolides produced by several Streptomyces species, including Streptomyc es venezuelae ATCC 15439, which produces both 12-membered ring macrolides m ethymycin, neomethymycin, and 14-membered ring macrolides pikromycin and na rbomycin. Cloning and sequencing of the biosynthetic gene clusters for thes e macrolides from three selected Streptomyces strains revealed a common gen etic architecture of their polyketide syntheses (PKSs). Unlike PKS clusters of other 14-membered ring macrolides such as erythromycin and oleandomycin , each of the pikromycin series producers harbors a six module PKS cluster, in which modules 5 and 6 are encoded on two separate proteins instead of o ne bimodular protein, as well as a thioesterase II gene immediately downstr eam of the main PKS gene. The results shed new light on the evolution of mo dular PKSs and provide further evidence on the regulation of methymycin and pikromycin production in S. venezuelae ATCC 15439. (C) 2000 Elsevier Scien ce B.V. All rights reserved.