Nutrient regulation of epothilone biosynthesis in heterologous and native production strains.
Fermentation media with different initial concentrations of ammonium and phosphate salts were used to study the inhibitory effects of those ions on growth and production of epothilone in Sorangium cellulosum and Myxococcus xanthus. The native epothilone producer, S. cellulosum was more sensitive to ammonium and phosphate than the heterologous producer, M. xanthus. An ammonium concentration of 12 mM reduced epothilone titers by 90% in S. cellulosum but by only 40% in M. xanthus. When 5 mM phosphate was added to the medium, production in both strains was 60% lower. Higher phosphate concentrations had little additional effect on M. xanthus titers, but epothilone production with 17 mM extra-cellular phosphate in S. cellulosum was 95% lower than in the control condition. The effect of iron supplementation to the fermentation medium was also investigated. Both strains showed best production with 20 microM iron added to the medium.
Regentin
R
R
Department of Process Sciences, Kosan Biosciences, 3832 Bay Center Place, Hayward, CA 94545, USA. regentin@kosan.com
Frykman
S
S
Lau
J
J
Tsuruta
H
H
Licari
P
P
D000970:Antineoplastic Agents / Q000378:metabolism; D001709:Biotechnology; D003470:Culture Media; D034261:Epothilones / Q000096:biosynthesis*; D005285:Fermentation; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D009231:Myxococcales / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D016941:Myxococcus xanthus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D003470:Culture Media; D034261:Epothilones; D010710:Phosphates; D007501:Iron