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 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.
Frykman
S
S
Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, CA 94545, USA.
Tsuruta
H
H
Lau
J
J
Regentin
R
R
Ou
S
S
Reeves
C
C
Carney
J
J
Santi
D
D
Licari
P
P
D000085:Acetates / Q000378:metabolism; D001431:Bacteriological Techniques / Q000379:methods; D003470:Culture Media / Q000737:chemistry*; D007218:Industrial Microbiology / Q000379:methods*; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D016941:Myxococcus xanthus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism
D000085:Acetates; D003470:Culture Media; D018942:Macrolides; D011422:Propionates; C029658:propionic acid