Scheme 1 - Pikromycin biosynthesis and substrate mimics.
From the following article
Structural basis for macrolactonization by the pikromycin thioesterase
David L Akey, Jeffrey D Kittendorf, John W Giraldes, Robert A Fecik, David H Sherman & Janet L Smith
Nature Chemical Biology 2, 537 - 542 (2006) Published online: 10 September 2006
doi:10.1038/nchembio824
(a) Terminal steps of the pikromycin biosynthetic pathway in S. venezuelae ATCC 15439. Premature termination of polyketide biosynthesis after the steps catalyzed by PikAIII results in the generation of the 12-membered-ring macrolactone 10-deoxymethynolide (Compound 3), whereas continued elongation by PikAIV results in the biosynthesis of the 14-membered-ring macrolactone narbonolide (Compound 4). Further processing by the post-PKS tailoring enzymes DesVII, a glycosyltransferase, and PikC, a cytochrome P450 hydroxylase, completes the biosynthesis of the macrolide antibiotics methymycin and pikromycin, respectively3. (b) Hexaketide substrate mimics. (c) Diphenylphosphonate affinity labels. Ac, acetyl; Me, methyl; Ph, phenyl.
