基于微生物法甾体羟基化反应

doi:10.19586/j.2095-2341.2022.0001

生物技术进展 ›› 2022, Vol. 12 ›› Issue (4): 539-548.DOI: 10.19586/j.2095-2341.2022.0001

基于微生物法甾体羟基化反应

黄娟(), 朱惠萱, 田怀香, 于海燕, 陈臣, 荣绍丰()

上海应用技术大学香料香精化妆品学部，上海 201418

收稿日期:2022-01-05 接受日期:2022-01-28 出版日期:2022-07-25 发布日期:2022-08-10
通讯作者: 荣绍丰
作者简介:黄娟 E-mail：hjhuangjuan@126.com|；

Steroidal Hydroxylation Based on Microbial Method

Juan HUANG(), Huixuan ZHU, Huaixiang TIAN, Haiyan YU, Chen CHEN, Shaofeng RONG()

School of Perfume and Aroma，Shanghai Institute of Technology，Shanghai 201418，China

Received:2022-01-05 Accepted:2022-01-28 Online:2022-07-25 Published:2022-08-10
Contact: Shaofeng RONG

摘要/Abstract

摘要：

甾体化合物又称类固醇，是重要的药物活性成分和药物合成中间体，因其具有环戊烷多氢菲的基本骨架，反应类型丰富，其中羟基化反应因产品具有广阔的市场应用前景而受到广泛关注。羟基化反应有化学法和生物法两种，生物法具有区域和立体专一性、对映体专一性等特点而成为目前主要的生产方法。首先从反应原理、类型及机制3个方面介绍了甾体微生物羟基化过程；其次，基于文献及自身研究工作，从甾体羟基化反应的发酵条件、底物溶解性、跨膜运输及反应器内流体力学特性4个角度对羟基化过程的影响进行了综述；最后，基于甾体羟基化反应特性及当前研究进展，对该反应过程后续研究提出展望，旨在为后期甾体羟基化反应的相关研究提供一定参考依据。

关键词: 甾体, 羟基化, 底物溶解性, 跨膜运输, 流体力学特性

Abstract:

Steroids are important active components of drugs and intermediates in drug synthesis. There existed various transformations of steroids because of the basic skeleton of cyclopentane dihydrophenanthrene. Hydroxylation has attracted extensive attention on account of its broad market application prospect. There are two methods to accomplish hydroxylation： chemical method and biological method. Biological method has become the main production method due to its regio specificity， stereos-pecificity and enantiomeric specificity. In this article， firstly， the microbial hydroxylation process of steroids was introduced from three aspects： reaction principle， reaction type and reaction mechanism； secondly， the effect of fermentation conditions， substrate solubility， transmembrane transport and hydrodynamics in the reactor on the hydroxylation process were reviewed based on the research results of the literature and our own work； finally， the prospect was put forward based on the characteristics of the hydroxylation process and the present progress， aiming to provide some reference for the related research on the steroid hydroxylation in the future.

Key words: steroids, hydroxylation, substrate solubility, cell permeability, hydrodynamic characteristics

中图分类号:

O629

黄娟, 朱惠萱, 田怀香, 于海燕, 陈臣, 荣绍丰. 基于微生物法甾体羟基化反应[J]. 生物技术进展, 2022, 12(4): 539-548.

Juan HUANG, Huixuan ZHU, Huaixiang TIAN, Haiyan YU, Chen CHEN, Shaofeng RONG. Steroidal Hydroxylation Based on Microbial Method[J]. Current Biotechnology, 2022, 12(4): 539-548.

图/表 5

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羟基化反应类型	微生物	底物
1-α	斜卧青霉	4-雄甾烯-3，17-二酮
5-α	尖孢镰刀菌、甘蔗凤梨病菌、甄氏外瓶霉	孕烯醇酮、睾酮、孕酮、可的松、泼尼松
9-α	红平红球菌、分枝杆菌、山扁豆生棒孢	4-雄甾烯-3，17-二酮
11-α	赭曲霉	坎利酮、孕酮
14-α	Absidia regnieri菌、毛壳菌	黄体酮、雄烯二酮、孕烯
15-α	黄色镰刀菌、雷斯特里克(氏)青霉菌	孕甾酮、左旋乙基甾烯二酮
16-α	玫瑰产色链霉菌、黑根霉、赭曲霉	9α-氟氢可的松、黄体酮
17-α	绿色木霉、黑根霉、赭曲霉	孕甾酮、环氧黄体酮
2-β	白腐核盘霉	11-脱氢皮甾醇、黄体酮、17a-羟基孕酮
6-β	毛壳菌、赭曲霉	雄烯二酮、睾酮、孕酮、孕烯醇酮、脱氢表雄甾酮
11-β	短刺小克银汉霉、蓝色犁头霉、新月弯孢霉、赭曲霉、新月弯孢霉	环氧黄体酮、化合物S、皮质酮
15-β	巨大芽孢杆菌、白腐核盘霉	氯苯丙氨酸、黄体酮、17a-羟基孕酮
17-β	粗糙链孢霉	4-雄甾烯-3，17-二酮
19-角甲基	球墨孢霉、芝麻丝核菌	11-脱氢皮甾醇

羟基化反应类型	微生物	底物
1-α	斜卧青霉	4-雄甾烯-3，17-二酮
5-α	尖孢镰刀菌、甘蔗凤梨病菌、甄氏外瓶霉	孕烯醇酮、睾酮、孕酮、可的松、泼尼松
9-α	红平红球菌、分枝杆菌、山扁豆生棒孢	4-雄甾烯-3，17-二酮
11-α	赭曲霉	坎利酮、孕酮
14-α	Absidia regnieri菌、毛壳菌	黄体酮、雄烯二酮、孕烯
15-α	黄色镰刀菌、雷斯特里克(氏)青霉菌	孕甾酮、左旋乙基甾烯二酮
16-α	玫瑰产色链霉菌、黑根霉、赭曲霉	9α-氟氢可的松、黄体酮
17-α	绿色木霉、黑根霉、赭曲霉	孕甾酮、环氧黄体酮
2-β	白腐核盘霉	11-脱氢皮甾醇、黄体酮、17a-羟基孕酮
6-β	毛壳菌、赭曲霉	雄烯二酮、睾酮、孕酮、孕烯醇酮、脱氢表雄甾酮
11-β	短刺小克银汉霉、蓝色犁头霉、新月弯孢霉、赭曲霉、新月弯孢霉	环氧黄体酮、化合物S、皮质酮
15-β	巨大芽孢杆菌、白腐核盘霉	氯苯丙氨酸、黄体酮、17a-羟基孕酮
17-β	粗糙链孢霉	4-雄甾烯-3，17-二酮
19-角甲基	球墨孢霉、芝麻丝核菌	11-脱氢皮甾醇

基于微生物法甾体羟基化反应

Steroidal Hydroxylation Based on Microbial Method

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