Production of 7α,15α-diOH-DHEA from dehydroepiandrosterone by Colletotrichum lini ST-1 through integrating glucose-feeding with multi-step substrate addition strategy.
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.
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China.
Cong
C
Li
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China.
Hui
H
Li
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China.
Jin
J
Sun
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China.
XinYue
X
Zhang
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China.
Jinsong
J
Shi
School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People's Republic of China. zhenghxu@jiangnan.edu.cn.
Zhenghong
Z
Xu
D020231:Colletotrichum / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*
D003687:Dehydroepiandrosterone; D005947:Glucose
7α,15α-diOH-DHEA; Bioconversion; Colletotrichum lini; Glucose-feeding; Multi-step addition