文摘
Feeding experiments with isotope-labeled precursors rule out hydroxypyruvate and TCA cycleintermediates as the metabolic source of methoxymalonyl-ACP, the substrate for incorporation of "glycolate"units into ansamitocin P-3, soraphen A, and other antibiotics. They point to 1,3-bisphosphoglycerate asthe source of the methoxymalonyl moiety and show that its C-1 gives rise to the thioester carbonyl group(and hence C-1 of the "glycolate" unit), and its C-3 becomes the free carboxyl group of methoxymalonyl-ACP, which is lost in the subsequent Claisen condensation on the type I modular polyketide synthases(PKS). D-[1,2-13C2]Glycerate is also incorporated specifically into the "glycolate" units of soraphen A, butnot of ansamitocin P-3, suggesting differences in the ability of the producing organisms to activate glycerate.A biosynthetic pathway from 1,3-bisphosphoglycerate to methoxymalonyl-ACP is proposed. Two newsyntheses of R- and S-[1,2-13C2]glycerol were developed as part of this work.