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Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase

文献类型：期刊论文

作者Liang, Bo1,2; Huang, Xuenian1; Teng, Yun3; Liang, Yajing1,4; Yang, Yong3; Zheng, Linghui3; Lu, Xuefeng1,4
刊名BIOTECHNOLOGY JOURNAL
出版日期2018-06-01
卷号13期号:6
关键词Aspergillus Terreus Directed Evolution Lovastatin Hydrolase Monacolin j Simvastatin
ISSN号1860-6768
DOI10.1002/biot.201800094
文献子类Article
英文摘要Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 degrees C increased T-50(10) over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete bioproduction of simvastatin at industrial scale.
WOS关键词DIRECTED EVOLUTION ; CLONOSTACHYS-COMPACTIUSCULA ; HIS-TAG ; DEHYDROGENASE ; ESTERASE ; SYNTHASE ; ACYLTRANSFERASE ; BIOSYNTHESIS ; BIOCATALYSIS ; SOLUBILITY
WOS研究方向Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology
语种英语
WOS记录号WOS:000434270100012
出版者WILEY-V C H VERLAG GMBH
资助机构Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJ-STS-ZDTP-031) ; National Natural Sciences Foundation of China(31400080) ; Hisun Pharmaceutical Co., Ltd. in China
源URL[http://ir.qibebt.ac.cn/handle/337004/11431]  
专题中国科学院青岛生物能源与过程研究所
通讯作者Lu, Xuefeng
作者单位1.Chinese Acad Sci, Shandong Prov Key Lab Synthet Biol, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Zhejiang Hisun Pharmaceut Co Ltd, Zhejiang Key Lab Antifungal Drugs, Taizhou 318000, Peoples R China
4.Chinese Acad Sci, Key Lab Biofuels, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Peoples R China
推荐引用方式
GB/T 7714		 Liang, Bo,Huang, Xuenian,Teng, Yun,et al. Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase[J]. BIOTECHNOLOGY JOURNAL,2018,13(6).
APA Liang, Bo.,Huang, Xuenian.,Teng, Yun.,Liang, Yajing.,Yang, Yong.,...&Lu, Xuefeng.(2018).Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase.BIOTECHNOLOGY JOURNAL,13(6).
MLA Liang, Bo,et al."Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase".BIOTECHNOLOGY JOURNAL 13.6(2018).

入库方式： OAI收割

来源：青岛生物能源与过程研究所

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