Acta Pharmaceutica, Vol. 71 No. 1, 2021.
Izvorni znanstveni članak
https://doi.org/10.2478/acph-2021-0004
Improved 11α-hydroxycanrenone production by modification of cytochrome P450 monooxygenase gene in Aspergillus ochraceus
QIANQIAN LI
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
LI SHI
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
YINGYING LIU
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
SHIMIN GUAN
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
SHUO ZHANG
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
BAOGUO CAI
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
SHAOFENG RONG
; Department of Bioengineering, Shanghai Institute of Technology, Fengxian, Shanghai, 201418, China
Sažetak
Eplerenone is a drug that protects the cardiovascular system. 11α-Hydroxycanrenone is a key intermediate in eplerenone synthesis. We found that although the cytochrome P450 (CYP) enzyme system in Aspergillus ochraceus strain MF018 could catalyse the conversion of canrenone to 11α-hydroxycanrenone, its biocatalytic efficiency is low. To improve the efficiency of 11α-hydroxycanrenone production, the CYP monooxygenase-coding gene of MF018 was predicted and cloned based on whole-genome sequencing results. A recombinant A. ochraceus strain MF010 with the high expression of CYP monooxygenase was then obtained through homologous recombination. The biocatalytic rate of this recombinant strain reached 93 % at 60 h without the addition of organic solvents or surfactants and was 17–18 % higher than that of the MF018 strain. Moreover, the biocatalytic time of the MF010 strain was reduced by more than 30 h compared with that of the MF018 strain. These results show that the recombinant A. ochraceus strain MF010 can overcome the limitation of substrate biocatalytic efficiency and thus holds a high potential for application in the industrial production of eplerenone.
Ključne riječi
Aspergillus ochraceus; P450 monooxygenase; homologous recombination; canrenone; 11α-hydroxycanrenone
Hrčak ID:
236062
URI
Datum izdavanja:
31.3.2021.
Posjeta: 1.007 *