Patent ID: 6858411
Filing Date: 2005-02-22
Classification: A61P,C07D,C12N,C12P

Abstract:
1. A method for preparing an epothilone D derivative having a methyl group at C-12 and a double bond between C-12 and C-13, which method comprises providing substrates including extender units to a non- S. cellulosum host cell that expresses a modified functional Sorangium cellulosum epothilone polyketide synthase (PKS), wherein said PKS comprises (a) replacement of at least one acyltransferase (AT) domain with an AT domain of different specificity in module 7 and/or module 8; inactivation of a ketoreductase (KR) domain in module 7; inactivation of a methyltransferase (MT) domain in module 8; and addition of at least one of KR, dehydrogenase (DH) and enoylreductase (ER) activity in at least one β-carbonyl modification domain in module 7 and/or module 8.