title: New insights into rifamycin B biosynthesis: isolation of proansamycin B and 34a-deoxy-rifamycin W as early macrocyclic intermediates indicating two separated biosynthetic pathways.
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.
authors.affiliation: Novartis Pharma AG, Research, Drug Discovery Center and Central Technologies, Basel, Switzerland.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Stratmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Schupp
authors.forename: Christiane
authors.initials: C
authors.lastname: Toupet
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schilling
authors.forename: Lukas
authors.initials: L
authors.lastname: Oberer
authors.forename: René
authors.initials: R
authors.lastname: Traber
mesh_terms: D000192:Actinomycetales / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012294:Rifamycins / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; C458979:proansamycin B; C033974:rifamycin B