Production of a novel polyketide through the construction of a hybrid polyketide synthase.
The lactone rings of the polyketides platenolide and tylactone are synthesized by condensation of acetate-, proprionate-, and butyrate-derived precursors. A hybrid tylactone/platenolide synthase was constructed to determine if the choice of substrate is programmed by the polyketide synthase and to ascertain if a substrate different than that normally used in the first step of platenolide synthesis could be incorporated into the final polyketide. In this work, we report the successful incorporation of a propionate in place of the acetate normally used in the first step of platenolide synthesis. This result demonstrates that polyketide synthases choose a particular substrate at defined steps and provides strong evidence that substrate choice is programmed by the acyl transferase domain of a large, multifunctional polyketide synthase.
Kuhstoss
S
S
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Huber
M
M
Turner
J R
JR
Paschal
J W
JW
Rao
R N
RN
D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D007783:Lactones / Q000378:metabolism*; D018942:Macrolides; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D017384:Sequence Deletion; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity; D015645:Tylosin / Q000031:analogs & derivatives / Q000096:biosynthesis
C103692:16-methylplatenolide I; D000214:Acyl Coenzyme A; D000900:Anti-Bacterial Agents; D007783:Lactones; D018942:Macrolides; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; C009061:propionyl-coenzyme A; C016675:platenolide I; D008316:Malonyl Coenzyme A; C027411:protylonolide; D000217:Acyltransferases; D015645:Tylosin