期刊
METABOLIC ENGINEERING
卷 15, 期 -, 页码 75-87出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2012.10.005
关键词
Cholesterol oxidase; Mycobacteria; Sterols; Androst-4-ene-3,17-dione; Androst-1,4-diene-3,17-dione
资金
- Fundamental Research Funds for the Central Universities of China [WF1114017]
- Postdoctoral Foundation of China [20100170757]
- National Special Fund for State Key Laboratory of Bioreactor Engineering [2060204]
- National Natural Science Foundation of China [21206039]
Mycobacteria have been modified to transform sterols to produce valuable steroids. Here, we demonstrated that the oxidation of sterols to sterones is a rate-limiting step in the catabolic pathway of sterols in Mycobacterium neoaurum. Two cholesterol oxidases ChoM1 and ChoM2 involved in the step were identified in M. neoaurum and the ChoM2 shared up to 45% identity with other cholesterol oxidases. We demonstrated that the combination of ChoM1 and ChoM2 plays a significant role in this step. Accordingly, we developed a strategy to overcome this rate-limiting step by augmenting the activity of cholesterol oxidases in M. neoaurum strains to enhance their transformation productivity of sterols to valuable steroids. Our results indicated that the augmentation of ChoM2 achieved 5.57 g/l androst-1,4-diene-3,17-dione in M. neoaurum NwIB-01 MS and 6.85 g/l androst-4-ene-3,17-dione in M. neoaurum NwIB-R10, greatly higher than the original yield, 3.87 g/l androst-1,4-diene-3,17-dione and 453 g/l androst-4-ene-3,17-dione, respectively. (C) 2012 Elsevier Inc. All rights reserved.
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