A new cytotoxic epothilone from modified polyketide synthases heterologously expressed in Myxococcus xanthus

J Nat Prod. 2002 Jul;65(7):1061-4. doi: 10.1021/np020120f.

Robert L Arslanian ¹, Li Tang, Shannon Blough, Wei Ma, Rong-Guo Qiu, Leonard Katz, John R Carney

Affiliations

Affiliation

1 Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, California 94545, USA.

PMID: 12141877 DOI: 10.1021/np020120f

Abstract

A new epothilone, 10,11-didehydroepothilone D (5), was isolated from a strain of the heterologous host Myxococcus xanthus genetically engineered to produce epothilone D (4). The structure of 5 was determined from NMR and MS data. The epothilone polyketide synthase was further modified in a recombinant M. xanthus strain to produce 5 as the major epothilone-related metabolite. The cytotoxicity of 5 against a panel of tumor cell lines, including several with multidrug resistance, and its effect on tubulin polymerization were comparable to epothilone D (4).

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