Pang Cuiping, Cao Yuting, Zhu Xiangdong
College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, China.
J Basic Microbiol. 2017 Jan;57(1):12-20. doi: 10.1002/jobm.201600191. Epub 2016 Sep 30.
Nowadays, there are a few steroid drugs or intermediates that have been obtained via the transformation of microorganisms, and many strains of transformed steroids have not been found yet. Therefore, it is very significant to screen for the strains that have the abilities to transform steroids to produce valuable products. This study has focused on the screen and identification of strains, the structural identification of converted products, and the optimization of transformation conditions, as well as the establishment of transformation systems. A soil microbiota was screened for strain involved in the biotransformation of steroids. A new isolate IS547 is capable of converting a variety of steroids (such as cholesterol, ergosterol, hydrocortisone, progesterone, pregnenolone, and 16,17-alpha-epoxypregnenolone). Based on the 18S rDNA gene sequence comparison, the isolate IS547 has been demonstrated to be very closely related to Cladosporium sp. genus. Present paper is the first report regarding the microbial transformation by Cladosporium sp. to produce active intermediates, which include 7-hydroxy cholesterol, 20-droxyl-16α,17α-epoxypregna-4-dien-3-one, 7-ketocholesterol, and 7-droxyl-16α,17α-epoxypregna-4-dien-3,20-dione. Under the optimum conditions, the yields of product 3 and product 4 were 20.58 and 17.42%, respectively, higher than that prior to the optimization. The transformation rate increased significantly under the optimum fermentation conditions. This study describes an efficient, rapid, and inexpensive biotransformation system for the production of active pharmaceutical intermediates.
如今,已有一些甾体药物或中间体是通过微生物转化获得的,还有许多转化甾体的菌株尚未被发现。因此,筛选具有转化甾体以生产有价值产品能力的菌株具有重要意义。本研究聚焦于菌株的筛选与鉴定、转化产物的结构鉴定、转化条件的优化以及转化体系的建立。从土壤微生物群落中筛选参与甾体生物转化的菌株。新分离出的IS547菌株能够转化多种甾体(如胆固醇、麦角固醇、氢化可的松、孕酮、孕烯醇酮和16,17-α-环氧孕烯醇酮)。基于18S rDNA基因序列比较,已证明分离株IS547与枝孢属密切相关。本文是关于枝孢属微生物转化生产活性中间体的首次报道,这些活性中间体包括7-羟基胆固醇、20-羟基-16α,17α-环氧孕甾-4-烯-3-酮、7-酮胆固醇和7-羟基-16α,17α-环氧孕甾-4-烯-3,20-二酮。在最佳条件下,产物3和产物4的产率分别为20.58%和17.42%,高于优化前。在最佳发酵条件下,转化率显著提高。本研究描述了一种用于生产活性药物中间体的高效、快速且廉价的生物转化体系。