Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus
文献类型：期刊论文
| 作者 | Huang, Xuenian1,2,3 ; Liang, Yajing1,2; Yang, Yong4; Lu, Xuefeng1,2
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| 刊名 | METABOLIC ENGINEERING
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| 出版日期 | 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 |
| 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. |
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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