Production of 7α,15α-diOH-DHEA from dehydroepiandrosterone by Colletotrichum lini ST-1 through integrating glucose-feeding with multi-step substrate addition strategy

Autor: XinYue Zhang, Cong Li, Zhenghong Xu, Jin-Song Shi, Sun Jin, Hui Li
Rok vydání: 2016
Předmět:
Zdroj: Bioprocess and Biosystems Engineering. 39:1259-1266
ISSN: 1615-7605
1615-7591
Popis: Hydroxylation of dehydroepiandrosterone (DHEA) to 3β,7α,15α-trihydroxy-5-androstene-17-one (7α,15α-diOH-DHEA) by Colletotrichum lini ST-1 is an essential step in the synthesis of many steroidal drugs, while low DHEA concentration and 7α,15α-diOH-DHEA production are tough problems to be solved urgently in industry. In this study, the significant improvement of 7α,15α-diOH-DHEA yield in 5-L stirred fermenter with 15 g/L DHEA was achieved. To maintain a sufficient quantity of glucose for the bioconversion, glucose of 15 g/L was fed at 18 h, the 7α,15α-diOH-DHEA yield and dry cell weight were increased by 17.7 and 30.9 %, respectively. Moreover, multi-step DHEA addition strategy was established to diminish DHEA toxicity to C. lini, and the 7α,15α-diOH-DHEA yield raised to 53.0 %. Further, a novel strategy integrating glucose-feeding with multi-step addition of DHEA was carried out and the product yield increased to 66.6 %, which was the highest reported 7α,15α-diOH-DHEA production in 5-L stirred fermenter. Meanwhile, the conversion course was shortened to 44 h. This strategy would provide a possible way in enhancing the 7α,15α-diOH-DHEA yield in pharmaceutical industry.
Databáze: OpenAIRE