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

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Abstract

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.

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Acknowledgments

This work is financially supported by the National High-Tech R&D Program (No. 2011AA02A211) and the National Natural Science Foundation of China (No. 31300026).

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Authors and Affiliations

  1. School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Avenue, 214122, Wuxi, People’s Republic of China

    Cong Li, Hui Li, Jin Sun, XinYue Zhang, Jinsong Shi & Zhenghong Xu

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  1. Cong Li
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  2. Hui Li
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  3. Jin Sun
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  4. XinYue Zhang
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  5. Jinsong Shi
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Correspondence to Zhenghong Xu.

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Li, C., Li, H., Sun, J. et al. Production of 7α,15α-diOH-DHEA from dehydroepiandrosterone by Colletotrichum lini ST-1 through integrating glucose-feeding with multi-step substrate addition strategy. Bioprocess Biosyst Eng 39, 1259–1266 (2016). https://doi.org/10.1007/s00449-016-1604-y

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  • DOI: https://doi.org/10.1007/s00449-016-1604-y

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