Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus

doi:10.1016/j.ymben.2017.06.005

CORC > 青岛生物能源与过程研究所 > 中国科学院青岛生物能源与过程研究所 > 微生物代谢工程团队

	Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus
	Huang, Xuenian 1,2,3; Liang, Yajing 1,2; Yang, Yong 4; Lu, Xuefeng 1,2
刊名	METABOLIC ENGINEERING
	2017-07-01
卷号	42 页码:109-114
关键词	Monacolin j Simvastatin Lovastatin Hydrolase Aspergillus Terreus Microbial Cell Factory
DOI	10.1016/j.ymben.2017.06.005
文献子类	Article
英文摘要	Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
WOS关键词	POLYKETIDE SYNTHASE ; CLONOSTACHYS-COMPACTIUSCULA ; LOVASTATIN BIOSYNTHESIS ; SYNTHETIC BIOLOGY ; ESCHERICHIA-COLI ; SYSTEMS BIOLOGY ; ACYLTRANSFERASE ; MEVINOLIN ; REDUCTASE ; ESTERASE
WOS研究方向	Biotechnology & Applied Microbiology
语种	英语
WOS记录号	WOS:000405854400013
资助机构	National Natural Science 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/337004/9614]
专题	青岛生物能源与过程研究所_微生物代谢工程团队
作者单位	1.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Key Lab Biofuels, 189 Songling Rd, Qingdao 266101, Peoples R China 2.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Shandong Prov Key Lab Synthet Biol, 189 Songling Rd, Qingdao 266101, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Zhejiang Hisun Pharmaceut Co Ltd, 46 Waisha Rd, Taizhou City 318000, Peoples R China
推荐引用方式 GB/T 7714	Huang, Xuenian,Liang, Yajing,Yang, Yong,et al. Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus[J]. METABOLIC ENGINEERING,2017,42:109-114.
APA	Huang, Xuenian,Liang, Yajing,Yang, Yong,&Lu, Xuefeng.(2017).Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus.METABOLIC ENGINEERING,42,109-114.
MLA	Huang, Xuenian,et al."Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus".METABOLIC ENGINEERING 42(2017):109-114.