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Production of 5α-androstene-3,17-dione from phytosterols by co-expression of 5α-reductase and glucose-6-phosphate dehydrogenase in engineered Mycobacterium neoaurum

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논문

Production of 5α-androstene-3,17-dione from phytosterols by co-expression of 5α-reductase and glucose-6-phosphate dehydrogenase in engineered Mycobacterium neoaurum

학술지

Green chemistry : an international journal and green chemistry resource : GC

저자명

Zhao, Yunqiu; Shen, Yanbing; Ma, Sai; Luo, Jianmei; Ouyang, Wei; Zhou, Haijie; Tang, Rui; Wang, Min

초록

<P>5&alpha;-Androstene-3,17-dione (5&alpha;-AD), an important intermediate in the synthesis of steroid drugs, is mainly synthesized by chemical methods in industry. In this work, a new biotechnological production method of 5&alpha;-AD from cheap precursors had been developed. 5&alpha;-Reductase from <I>Treponema denticola</I>, which can convert the 3-oxo-4-ene structure into 5&alpha;-reductase products, was screened and expressed in <I>MNR</I> M3&Delta;<I>ksdd</I>, a major AD-producing strain. The engineered <I>MNR</I> M3&Delta;<I>ksdd</I>/261-<I>5&alpha;</I><SUB><I>T. denticola</I></SUB> strain showed a remarkably efficient one-step transformation of phytosterols (PS) into 5&alpha;-AD. As a cofactor for the reaction of 5&alpha;-reductase, nicotinamide adenine dinucleotide phosphate (NADPH) was supplied by the overexpression of glucose-6-phosphate dehydrogenase (G6PDH) in <I>MNR</I> M3&Delta;<I>ksdd.</I> Finally, the conversion increased from 67.9% to 86.4% in the cofactor recycling system. This study is the first to report the transformation of PS into 5&alpha;-AD by biological methods with a considerable yield. The present study also revealed that the engineered <I>M. neoaurum</I> containing 5&alpha;-reductase and G6PDH shows a practical value in producing 5&alpha;-AD in industry and provides a reference for the industrial production of high value products from cheap raw materials.</P><P>Graphic Abstract</P><P>5&alpha;-Androstene-3,17-dione (5&alpha;-AD), an important intermediate in the synthesis of steroid drugs, is mainly synthesized by chemical methods in industry.<BR/><IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c8gc03489c'/><BR/></P>

발행연도

2019

발행기관

The Royal Society of Chemistry

ISSN

1463-9262

ISSN

1463-9270

21

7

페이지

pp.1809-1815

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논문; 2019-12-31

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