On the Biosynthetic Origin of Methoxymalonyl-Acyl Carrier Protein, the Substrate for Incorporation of "Glycolate" Units into Ansamitocin and Soraphen A

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• 作者：Silke C. Wenzel ; Rachel M. Williamson ; Christian Grü ; nanger ; Jun Xu ; Klaus Gerth ; Rodolfo A. Martinez ; Steven J. Moss ; Brian J. Carroll ; Stephanie Grond ; Clifford J. Unkefer ; Rolf Mü ; ller ; Hein
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：November 8, 2006
• 年：2006
• 卷：128
• 期：44
• 页码：14325 - 14336
• 全文大小：857K
• 年卷期：v.128,no.44(November 8, 2006)
• ISSN：1520-5126

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.