title: Epoxyquinone formation catalyzed by a two-component flavin-dependent monooxygenase involved in biosynthesis of the antibiotic actinorhodin.
abstract: The biosynthetic gene cluster of the aromatic polyketide antibiotic actinorhodin (ACT) in Streptomyces coelicolor A3(2) carries a pair of genes, actVA-ORF5 and actVB, that encode a two-component flavin-dependent monooxygenase (FMO). Our previous studies have demonstrated that the ActVA-ORF5/ActVB system functions as a quinone-forming C-6 oxygenase in ACT biosynthesis. Furthermore, we found that this enzyme system exhibits an additional oxygenation activity with dihydrokalafungin (DHK), a proposed intermediate in the ACT biosynthetic pathway, and generates two reaction products. These compounds were revealed to be monooxygenated derivatives of kalafungin, which is spontaneously formed through oxidative lactonization of DHK. Their absolute structures were elucidated from their NMR spectroscopic data and by computer modeling and X-ray crystallography as (5S,14R)-epoxykalafungin and (5R,14S)-epoxykalafungin, demonstrating an additional epoxyquinone-forming activity of the ActVA-ORF5/ActVB system in vitro.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Taguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kimiko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Koji
authors.initials: K
authors.lastname: Ichinose
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004852:Epoxy Compounds / Q000737:chemistry*; D005415:Flavins / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008958:Models, Molecular; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D004852:Epoxy Compounds; D005415:Flavins; D006899:Mixed Function Oxygenases; D011809:Quinones; C013390:actinorhodin; D000095622:Benzoisochromanequinones