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  • On the biosynthetic origin of methoxymalonyl-acyl carrier protein, the substrate for incorporation of "glycolate" units into ansamitocin and soraphen A.

On the biosynthetic origin of methoxymalonyl-acyl carrier protein, the substrate for incorporation of "glycolate" units into ansamitocin and soraphen A.

Journal of the American Chemical Society (2006-11-02)
Silke C Wenzel, Rachel M Williamson, Christian Grünanger, Jun Xu, Klaus Gerth, Rodolfo A Martinez, Steven J Moss, Brian J Carroll, Stephanie Grond, Clifford J Unkefer, Rolf Müller, Heinz G Floss
RESUMEN

Feeding experiments with isotope-labeled precursors rule out hydroxypyruvate and TCA cycle intermediates 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 as the 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-(13)C(2)]Glycerate is also incorporated specifically into the "glycolate" units of soraphen A, but not 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 new syntheses of R- and S-[1,2-(13)C(2)]glycerol were developed as part of this work.

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Sigma-Aldrich
β-Hydroxypyruvic acid, ≥95.0% (dry substance, T)
Sigma-Aldrich
Lithium β-hydroxypyruvate hydrate, ≥97.0% (calc. based on dry substance, NT)
Sigma-Aldrich
Ansamitocin P-3 from Actinosynnema pretiosum, ≥90% (HPLC)