Elucidating the Mechanism of cis Double Bond Formation in Epothilone Biosynthesis.

Epothilones A (1) and B (2), and their late-stage biosynthetic intermediates, epothilones C (3) and D (4), are a new class of naturally occurring microtubule depolymerization inhibitors with potent antitumor activity. Epothilones D, B, and a derivative of B, are currently undergoing clinical trials. When moved into heterologous hosts, the six epothilone genes directed the production of epothilones C and D; addition of the adjacent gene epoK resulted in formation of epothilones A and B.