Dong Yang, Fei Ye, Christiana N. Teijaro, Dobeen Hwang, Thibault Annaval, Ajeeth Adhikari, Gengnan Li, Xiaohui Yan, Chun Gui, Christoph Rader, Ben Shen*
{"title":"细胞色素P450羟化酶YpmL在杨浦霉素A生物合成中的功能表征及其在蒽醌融合烯二炔结构多样化中的应用","authors":"Dong Yang, Fei Ye, Christiana N. Teijaro, Dobeen Hwang, Thibault Annaval, Ajeeth Adhikari, Gengnan Li, Xiaohui Yan, Chun Gui, Christoph Rader, Ben Shen*","doi":"10.1021/acs.orglett.2c00009","DOIUrl":null,"url":null,"abstract":"<p >Comparative analyses of four anthraquinone-fused enediyne biosynthetic gene clusters (BGCs) identified YpmL as a cytochrome P450 enzyme unique to the yangpumicin (YPM) BGC. In vitro characterization of YpmL established it as a hydroxylase, catalyzing C-6 hydroxylation in YPM A biosynthesis. In vivo application of YpmL enabled engineered production of four new tiancimycin analogues (<b>14</b>–<b>17</b>). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure–activity relationship.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"24 5","pages":"1219–1223"},"PeriodicalIF":5.0000,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.orglett.2c00009","citationCount":"3","resultStr":"{\"title\":\"Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification\",\"authors\":\"Dong Yang, Fei Ye, Christiana N. Teijaro, Dobeen Hwang, Thibault Annaval, Ajeeth Adhikari, Gengnan Li, Xiaohui Yan, Chun Gui, Christoph Rader, Ben Shen*\",\"doi\":\"10.1021/acs.orglett.2c00009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Comparative analyses of four anthraquinone-fused enediyne biosynthetic gene clusters (BGCs) identified YpmL as a cytochrome P450 enzyme unique to the yangpumicin (YPM) BGC. In vitro characterization of YpmL established it as a hydroxylase, catalyzing C-6 hydroxylation in YPM A biosynthesis. In vivo application of YpmL enabled engineered production of four new tiancimycin analogues (<b>14</b>–<b>17</b>). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure–activity relationship.</p>\",\"PeriodicalId\":54,\"journal\":{\"name\":\"Organic Letters\",\"volume\":\"24 5\",\"pages\":\"1219–1223\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2022-01-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/pdf/10.1021/acs.orglett.2c00009\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.orglett.2c00009\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.orglett.2c00009","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification
Comparative analyses of four anthraquinone-fused enediyne biosynthetic gene clusters (BGCs) identified YpmL as a cytochrome P450 enzyme unique to the yangpumicin (YPM) BGC. In vitro characterization of YpmL established it as a hydroxylase, catalyzing C-6 hydroxylation in YPM A biosynthesis. In vivo application of YpmL enabled engineered production of four new tiancimycin analogues (14–17). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure–activity relationship.
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.