南京大学戈惠明团队报道了NADPH依赖的酮还原酶催化教酒菌素生物合成中四环到五环的骨架重排。相关研究成果于2021年9月30日发表在《德国应用化学》。
氧化还原修饰酶在产生II型聚酮类化合物的结构复杂性和多样性方面起着关键作用。在教酒菌素生物合成中,早期的13C标记实验和生物信息学分析表明,该不寻常的苷元来自四环蒽环聚酮。
该文中,研究人员证明了碳骨架从线性蒽环聚酮到角五环生物合成中间体的重排需要两种氧化还原酶。黄素依赖性单加氧酶ChaZ催化拜尔-维利格氧化反应,在间苯二酚C上形成七元内酯。随后,酮还原酶ChaE以NADPH依赖的方式重新排列碳骨架并提供含α-吡喃酮的五环中间体,可能通过包括内酯羰基还原、羟醛型反应,随后自发形成γ-内酯环和芳构化的级联反应。
该工作揭示了一种前所未有的酮还原酶的功能,有助于产生芳香族聚酮化合物的结构复杂性。
附:英文原文
Title: An NADPH-dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis
Author: Hui Ming Ge, Fang Wen Jiao, Yi Shuang Wang, Xue Ting You, Wanqing Wei, Yu Chen, Cheng Long Yang, Zhi Kai Guo, Bo Zhang, Yong Liang, Ren Xiang Tan, Rui Hua Jiao
Issue&Volume: 2021-09-30
Abstract: Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13 C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and afford the α-pyrone containing pentacyclic intermediate in an NADPH-dependent manner, presumably via a cascade reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous γ-lactone ring formation, and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide.
DOI: 10.1002/anie.202112047
Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202112047
Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx