Biocatalytic Synthesis of Corticosteroid Derivatives by Toad-Derived Steroid C21-Hydroxylase

IF 5 1区化学 Q1 CHEMISTRY, ORGANIC Organic Letters Pub Date : 2025-04-17 DOI:10.1021/acs.orglett.5c00639

Meiling Duan, Xueqing Zhong, Jiaxu Qin, Guo-Qiang Lin, Qing-Li He, Qunfei Zhao

引用次数: 0

Abstract

CsCYP21A, a steroid 21-hydroxylase from Bufo bufo gargarizans, exhibits unprecedented sequential oxidations. Optimizing Pichia pastoris biotransformation conditions enhanced C21-hydroxylation selectivity, converting 14 substrates to 21-hydroxylated products, with 10 conversions of >80% and 4 yields of >80%. Hydrocortisone production reached 1.5 g L^–1 day^–1 with 100 g/L wet biomass. CsCYP21A’s versatility enables integration into the synthesis of over 10 steroidal drugs, offering a sustainable biocatalytic platform for green pharmaceutical manufacturing.

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蟾蜍衍生类固醇c21 -羟化酶生物催化合成皮质类固醇衍生物

CsCYP21A是一种来自巨蟒的甾体21-羟化酶，表现出前所未有的连续氧化。优化毕赤酵母的生物转化条件提高了c21 -羟基化的选择性，将14个底物转化为21-羟基化产物，其中10个转化率为80%，4个产率为80%。氢化可的松产量达到1.5 g L - 1 day-1，湿生物量为100 g/L。CsCYP21A的多功能性可以集成到10多种甾体药物的合成中，为绿色制药制造提供了可持续的生物催化平台。

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来源期刊

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.