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-did...

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Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2003-10, Vol.66 (10), p.1313-1317
Main Authors: STARKS, Courtney M., ZHOU, Yiqing, LIU, Fenghua, LICARI, Peter J.
Format: Article
Language:English
Subjects:
4-desmethyl-10,11-didehydroepothilone D
Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Applied microbiology
Biological and medical sciences
Cell Line, Tumor - drug effects
Chemotherapic agents
Drug Resistance, Multiple - drug effects
Drug Screening Assays, Antitumor
Epothilones - chemistry
Epothilones - isolation & purification
Epothilones - pharmacology
Fermentation
Fundamental and applied biological sciences. Psychology
Humans
Inhibitory Concentration 50
Microbiology
Molecular Structure
Myxococcus xanthus
Myxococcus xanthus - chemistry
Nuclear Magnetic Resonance, Biomolecular
polyketide synthase
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Summary: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.
ISSN:0163-3864
1520-6025
DOI:10.1021/np030218+