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利用未经处理的甘蔗糖蜜通过重组分枝杆菌生产雄烯二酮和 9α-羟基雄烯二酮。

Economical production of androstenedione and 9α-hydroxyandrostenedione using untreated cane molasses by recombinant mycobacteria.

机构信息

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China; College of Life Science, Liaocheng University, Liaocheng, Shandong 252059, China.

出版信息

Bioresour Technol. 2019 Oct;290:121750. doi: 10.1016/j.biortech.2019.121750. Epub 2019 Jul 9.

Abstract

Production of androstenedione (AD) and 9α-hydroxyandrostenedione (9α-OH-AD) by recombinant mycobacteria using untreated cane molasses and hydrolysate of mycobacterial cells (HMC) was investigated for the first time. B-vitamins feeding experiment and reverse transcription-PCR analysis showed that propionyl-CoA carboxylase (PCC) plays an important role in the phytosterol biotransformation of mycobacteria. The respective AD and 9α-OH-AD conversion ratios were increased by 2.91 and 1.48 times through coexpression of PCC and NADH dehydrogenase. The highest conversion ratios of AD and 9α-OH-AD obtained by using a co-feeding strategy of cane molasses and HMC reached 96.38% and 95.04%, respectively, and the total costs of carbon and nitrogen sources for the culture medium were reduced by 29.89% and 49.49%, respectively. Taking the results together, untreated cane molasses and HMC can be used for the economical production of steroidal pharmaceutical precursors by mycobacteria. This study offers an economical and green strategy for steroidal pharmaceutical precursor production.

摘要

首次研究了利用未经处理的甘蔗糖蜜和分枝杆菌细胞水解物(HMC)生产雄烯二酮(AD)和 9α-羟基雄烯二酮(9α-OH-AD)的重组分枝杆菌。B 族维生素喂养实验和反转录-PCR 分析表明,丙酰辅酶 A 羧化酶(PCC)在分枝杆菌植物甾醇生物转化中起着重要作用。通过共表达 PCC 和 NADH 脱氢酶,AD 和 9α-OH-AD 的转化率分别提高了 2.91 倍和 1.48 倍。使用甘蔗糖蜜和 HMC 的共喂养策略,AD 和 9α-OH-AD 的最高转化率分别达到 96.38%和 95.04%,培养基中碳源和氮源的总成本分别降低了 29.89%和 49.49%。综上所述,未经处理的甘蔗糖蜜和 HMC 可用于分枝杆菌经济地生产甾体药物前体。本研究为甾体药物前体的生产提供了一种经济、绿色的策略。

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