Modulation of epothilone analog production through media design

Recently, the epothilone polyketide synthase (PKS) was successfully introduced into a heterologous production host for the large-scale production of epothilone D. We have found that at least three other epothilones can also be produced as the major fermentation product of this recombinant strain by...

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Bibliographic Details
Published in:Journal of industrial microbiology & biotechnology 2002, Vol.28 (1), p.17-20
Main Authors: FRYKMAN, S, TSURUTA, H, LAU, J, REGENTIN, R, OU, S, REEVES, C, CARNEY, J, SANTI, D, LICARI, P
Format: Article
Language:English
Subjects:
Acetates - metabolism
Bacteriological Techniques - methods
Biological and medical sciences
Biotechnology
Culture Media - chemistry
epothilone D
Fermentation
Fundamental and applied biological sciences. Psychology
Genetic engineering
Industrial Microbiology - methods
Macrolides - chemistry
Macrolides - metabolism
Microbiology
Molecular Structure
Myxococcus xanthus - enzymology
Myxococcus xanthus - genetics
Myxococcus xanthus - metabolism
polyketide synthase
Propionates - metabolism
Studies
Sulfur
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Summary:Recently, the epothilone polyketide synthase (PKS) was successfully introduced into a heterologous production host for the large-scale production of epothilone D. We have found that at least three other epothilones can also be produced as the major fermentation product of this recombinant strain by supplementation of specific substrates to the production media. Addition of acetate or propionate to the media results in modulation of the epothilone D:C ratio, whereas addition of L-serine with either acetate or propionate yields epothilone H(1) or H(2) as the major product. This strategy permits production of at least four novel epothilones by culturing a single host with a genetically modified epothilone PKS in various media.
ISSN:1367-5435
1476-5535
DOI:10.1038/sj/jim/7000209