题目: Discovery of an Unexpected 1,4-Oxazepine-Linked seco-Fluostatin Heterodimer by Inactivation of the Oxidoreductase-Encoding Gene flsP

作者: Chunshuai Huang, Chunfang Yang, Wenjun Zhang，LipingZhang, Yiguang Zhu, Changsheng Zhang

刊物: The Journal of  Nature Products

年卷期页: 2021

摘要：Fluostatins belong to the atypical angucyclinone aromatic polyketides featuring a distinctive tetracyclic benzo[a]fluorene skeleton. To understand the formation of the heavily oxidized A-ring in fluostatins, a flavin adenine dinucleotide-binding oxidoreductase-encoding gene flsP was inactivated, leading to the production of an unprecedented 1,4-oxazepine-linked seco-fluostatin heterodimer difluostatin I (7) and five new fluostatin-related derivatives, fluostatins T–X (8–12). Their structures were elucidated by mass spectrometry, nuclear magnetic resonance, X-ray diffraction analysis, and biosynthetic considerations. Difluostatin I (7) represents the first example with an A-ring-cleaved 3′,4′-seco-fluostatin skeleton. The absolute configuration of fluostatin T (8) was determined by X-ray diffraction analysis. Fluostatin W (11) contains an uncommon isoxazolinone ring. These findings highlight the structural diversity of fluostatins.