title: Biosynthesis of hibarimicins. II. Elucidation of biosynthetic pathway by cosynthesis using blocked mutants.
abstract: The biosynthetic pathway of hibarimicin (HBM) was proposed on the basis of the experimental results obtained by using blocked mutants of Microbispora rosea subsp. hibaria TP-A0121, the HBM producer. In its biosynthesis, the oxidative coupling of the aromatic undecaketide unit generates a symmetrical aglycon HMP-Y1 (hibarimicin-mutant product Y1), which is oxidatively modified to hibarimicinone, the HBM aglycon. The following glycosylation of hibarimicinone gives rise to the HBM complex. We identified that HMP-Y1 prepared by methanolysis of HMP-Y6, a glycosylated metabolite from a blocked mutant, was the key intermediate: transformation of 13C-labeled HMP-Y1 to HBM B was confirmed by NMR measurements. Mutant strain produced another type of aglycon HMP-P1 in which the coupled polyketide units were intramolecularly bridged by the ether bond. This metabolite also arose by the spontaneous elimination of methanol molecule from hibarimicinone.
authors.affiliation: Biotechnology Research Center, Toyama Prefectural University, Kosugi, Toyama, Japan. takayuki_kajiura@ajinomoto.com
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kajiura
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Furumai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hori
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Higashi
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ishiyama
authors.forename: Masakazu
authors.initials: M
authors.lastname: Uramoto
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Oki
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid
chemical_list: D000900:Anti-Bacterial Agents