Involvement of the Baeyer–Villiger Monooxygenase IfnQ in the Biosynthesis of Isofuranonaphthoquinone Scaffold of JBIR‐76 and ‐77. (9th May 2016)

• Record Type: Journal Article
• Authors: Katsuyama, Yohei; Sone, Kaoru; Satou, Ryutaro; Izumikawa, Miho; Takagi, Motoki; Fujie, Manabu; Satoh, Noriyuki; Shin‐ya, Kazuo; Ohnishi, Yasuo
• Is Part Of: Chembiochem. Volume 17:Number 11(2016)
• Page Start: 1021
• Page End: 1028
• Publication Date: 2016-05-09
• Subjects: Baeyer–Villiger monooxygenase -- C−C bond cleavage -- isofuranonaphthoquinone -- natural products -- polyketides -- Streptomyces; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600095
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: JBIR‐76 and ‐77 are isofuranonaphthoquinones (IFNQs) isolated from Streptomyces sp. RI‐77. Draft genome sequencing and gene disruption analysis of Streptomyces sp. RI‐77 showed that a type II polyketide synthase (PKS) gene cluster ( ifn cluster) was responsible for the biosynthesis of JBIR‐76 and ‐77. It was envisaged that an octaketide intermediate (C16 ) could be synthesized by the minimal PKS (IfnANO) and that formation of the IFNQ scaffold (C13 ) would therefore require a C−C bond cleavage reaction. An ifnQ disruptant accumulated some shunt products (C15 ), which were presumably produced by spontaneous cyclization of the decarboxylated octaketide intermediate. Recombinant IfnQ catalyzed the Baeyer–Villiger oxidation of 1‐(2‐naphthyl)acetone, an analogue of the bicyclic octaketide intermediate. Based on these results, we propose a pathway for the biosynthesis of JBIR‐76 and ‐77, involving IfnQ‐catalyzed C−C bond cleavage as a key step in the formation of the IFNQ scaffold. Abstract : JBIR‐76 and ‐77 are isofuranonaphthoquinones isolated from Streptomyces sp. RI‐77. We have identified the JBIR‐76 and ‐77 biosynthesis gene cluster ( ifn cluster) and elucidated the critical role of the Baeyer–Villiger monooxygenase IfnQ in the construction of the isofuranonaphthoquinone scaffold.