Isolation and characterization of new epothilone analogues from recombinant Myxococcus xanthus fermentations.
Nine new epothilone analogues (6-8, 10, 11a, 11b, 12, 13, and 15) were isolated from fermentations of Myxococcus xanthus strains engineered with modified polyketide synthase genes. The epothilone structures were elucidated primarily through interpretation of 1D and 2D NMR data. 4-Desmethyl-10,11-didehydroepothilone D (6) displayed activity against several tumor cell lines, including a multi-drug-resistant cell line.
Starks
Courtney M
CM
Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, California 94545, USA.
Zhou
Yiqing
Y
Liu
Fenghua
F
Licari
Peter J
PJ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D016941:Myxococcus xanthus / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular
D000970:Antineoplastic Agents; D034261:Epothilones