5α-还原酶突变体及其在甾体C4,5位加氢药物中间体合成中的应用

By mutating specific amino acid sequences of 5α-reductase, a highly efficient 5α-reductase mutant was constructed, solving the problems of low conversion rate and environmental hazards of steroid drug intermediates in existing technologies, and realizing efficient and green synthesis of steroid drug intermediates.

CN121780465BActive Publication Date: 2026-07-17TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI +1

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
TIANJIN INST OF IND BIOTECH CHINESE ACADEMY OF SCI
Filing Date
2026-03-04
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

In existing technologies, the activity of 5α-reductase is low, resulting in low conversion and yield of steroidal drug intermediates. Furthermore, chemical and microbial fermentation methods pose environmental hazards and low efficiency.

Method used

By specifically mutating the amino acid sequence of 5α-reductase, especially modifying positions 56, 109, and/or 114, a highly efficient 5α-reductase mutant was constructed and combined with glucose-6-phosphate dehydrogenase to achieve efficient conversion at substrate concentrations up to 10 g/L.

Benefits of technology

It significantly improves the catalytic performance of 5α-reductase, especially achieving a 99% conversion rate for AD, shortening the conversion cycle, meeting the needs of industrial production, avoiding environmental hazards, and featuring a simple process suitable for large-scale production.

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Abstract

本发明属于酶基因工程及酶工程技术领域,公开了一种5α‑还原酶突变体及其在甾体C4,5位加氢药物中间体合成中的应用。该突变体与野生型5α‑还原酶的氨基酸序列相比,在对应于SEQ ID NO.1所示氨基酸序列的以下位点存在至少两个位点的突变:第56位、第109位和 / 或第114位。所述突变体对3‑酮基甾体化合物具有高效催化活性,在高底物投料浓度下,获得高收率的目标产物,无副产物,转化率不低于99%。本发明还公开了突变体的编码基因、重组载体、工程菌及应用,其反应条件温和、工艺简洁、环境友好,有效克服传统方法缺陷,为甾体药物中间体绿色工业化生产提供技术支撑,应用前景广阔。
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