New insights into rifamycin B biosynthesis: isolation of proansamycin B and 34a-deoxy-rifamycin W as early macrocyclic intermediates indicating two separated biosynthetic pathways.

Ansgar Stratmann, Thomas Schupp, Christiane Toupet, Wolfgang Schilling, Lukas Oberer, René Traber

Index: J. Antibiot. 55(4) , 396-406, (2002)

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Abstract

Proansamycin B, the formerly postulated intermediate of rifamycin B biosynthesis, was isolated from cultures of the Amycolatopsis mediterranei mutant F1/24. The structure was determined using UV, IR, NMR and MS techniques. Biotransformation studies demonstrate that proansamycin B is an intermediate of a shunt pathway, a 8-deoxy variant, of rifamycin B biosynthesis leading to 8-deoxy-rifamycin B as the final product. In addition, 34a-deoxy-rifamycin W, the direct precursor of rifamycin W, could be isolated representing the earliest macrocyclic intermediate obtained so far in the biosynthetic route to rifamycin B. Furthermore, the new rifamycin W-28-desmethyl-28-carboxy and rifamycin W-hemiacetal, intermediates in the transformation sequence of rifamycin W to rifamycin S, were isolated. Application of proton NMR measurements (double resonance and ROESY experiments) on the latter compound indicated that the stereochemistry at the chiral center C-28 is R.