Jia-Liang Zhou, Qiu-Yue Nie, Xian-Feng Hou, Kuan Zheng, Ran Hong, Gong-Li Tang
{"title":"Multienzyme Cascade Catalyzed Skeleton Rearrangement in a Caged Polyketide Biosynthesis","authors":"Jia-Liang Zhou, Qiu-Yue Nie, Xian-Feng Hou, Kuan Zheng, Ran Hong, Gong-Li Tang","doi":"10.1021/acs.orglett.4c04412","DOIUrl":null,"url":null,"abstract":"Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through <i>in vivo</i> and <i>in vitro</i> experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling. Significantly, a short-chain dehydrogenase TjhD5 was discovered to play a multifunctional role for multistep reactions.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"6 1","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.orglett.4c04412","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through in vivo and in vitro experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling. Significantly, a short-chain dehydrogenase TjhD5 was discovered to play a multifunctional role for multistep reactions.
期刊介绍：
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
