New insights into rifamycin B biosynthesis: isolation of proansamycin B and 34a-deoxy-rifamycin W as early macrocyclic intermediates indicating two separated biosynthetic pathways.
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.
Stratmann
Ansgar
A
Novartis Pharma AG, Research, Drug Discovery Center and Central Technologies, Basel, Switzerland.
Schupp
Thomas
T
Toupet
Christiane
C
Schilling
Wolfgang
W
Oberer
Lukas
L
Traber
René
R
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
D000900:Anti-Bacterial Agents; D012294:Rifamycins; C458979:proansamycin B; C033974:rifamycin B