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

doi:10.1002/biot.201800094

	Enhanced Single-Step Bioproduction of the Simvastatin Precursor Monacolin J in an Industrial Strain of Aspergillus terreus by Employing the Evolved Lovastatin Hydrolase
	Liang, Bo 1,2; Huang, Xuenian 1; Teng, Yun 3; Liang, Yajing 1,4; Yang, Yong 3; Zheng, Linghui 3; Lu, Xuefeng 1,4
刊名	BIOTECHNOLOGY JOURNAL
	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
DOI	10.1002/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
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000434270100012
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
内容类型	期刊论文
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).