Functional Characterization of Cytochrome P450 Hydroxylase YpmL in Yangpumicin A Biosynthesis and Its Application for Anthraquinone-Fused Enediyne Structural Diversification

IF 5 1区 化学 Q1 CHEMISTRY, ORGANIC
Dong Yang, Fei Ye, Christiana N. Teijaro, Dobeen Hwang, Thibault Annaval, Ajeeth Adhikari, Gengnan Li, Xiaohui Yan, Chun Gui, Christoph Rader, Ben Shen*
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引用次数: 3

Abstract

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 (1417). Evaluation of their cytotoxicity against selected human cancer cell lines shed new insights into the enediyne structure–activity relationship.

Abstract Image

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
通过对4个蒽醌融合烯二炔生物合成基因簇(BGC)的比较分析,确定YpmL是杨浦霉素(YPM) BGC所特有的细胞色素P450酶。对YpmL的体外鉴定证实它是一种羟化酶,在YPM a的生物合成中催化C-6羟基化。在体内应用YpmL使四种新的天西霉素类似物的工程化生产成为可能(14-17)。它们对选定的人类癌细胞系的细胞毒性评价为研究烯二炔的构效关系提供了新的思路。
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来源期刊
Organic Letters
Organic Letters 化学-有机化学
CiteScore
9.30
自引率
11.50%
发文量
1607
审稿时长
1.5 months
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.
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