Isolation and characterization of the epothilone biosynthetic gene clusterfrom Sorangium cellulosum

The epothilone biosynthetic gene cluster was isolated from Sorangium cellul osum strain SMP44. The gene cluster contains seven genes and spans approx. 56 kb. The genes encoding the PKS, epoA, epoC, epoD, epoE, and epoF, are di vided into nine modules. The EpoB protein is a non-ribosomal peptide synthe tase (NRPS) that catalyzes formation of the thiazole found in the epothilon es. EpoK is a P450 enzyme responsible for the epoxidation of epothilones C and D to epothilones A and B, respectively. EpoK was expressed in Escherich ia coli, and the purified protein was shown to convert epothilone D to epot hilone B in vitro. (C) 2000 Elsevier Science B.V. All rights reserved.