Cloning and heterologous expression of the epothilone gene cluster

The polyketide epothilone is a potential anticancer agent that stabilizes m icrotubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacterium Sorangium cellulosum was clone d and completely sequenced. It encodes six multifunctional proteins compose d of a loading module, one nonribosomal peptide synthetase module, eight po lyketide synthase modules, and a P450 epoxidase that converts desoxyepothil one into epothilone. Concomitant expression of these genes in the actinomyc ete Streptomyces coelicolor produced epothilones A and B. Streptomyces coel icolor is more amenable to strain improvement and grows about 10-fold as ra pidly as the natural producer, so this heterologous expression system porte nds a plentiful supply of this important agent.