Protein Acylation Affects the Artificial Biosynthetic Pathway for Pinosylvin Production in Engineered E. coli
文献类型：期刊论文
| 作者 | Xu, Jun-Yu1,2,3; Xu, Ya2; Chu, Xiaohe1; Tan, Minjia3 ; Ye, Bang-Ce1,2
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| 刊名 | ACS CHEMICAL BIOLOGY
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| 出版日期 | 2018-05 |
| 卷号 | 13期号:5页码:1200-1208 |
| ISSN号 | 1554-8929 |
| DOI | 10.1021/acschembio.7b01068 |
| 文献子类 | Article; Proceedings Paper |
| 英文摘要 | The effect of regulatory system on the engineered biosynthetic pathway in chassis cells remains incompletely understood in microorganisms. Acyl-CoAs function as key precursors for the biosynthesis of various natural products and the dominant donors for protein acylation. The polyphenol pinosylvin, with high antimicrobial and antifungal activities, is biosynthesized with malonyl-CoA as its direct precursors. But correlation between lysine malonylation and pinosylvin biosynthesis remains unknown. Herein, we found that the malonyl-CoA-driven lysine malonylation plays an important role in interaction between the engineered pathway of pinosylvin synthesis and E. coli chassis cell. Oversupply of malonyl-CoA leads to an increase in malonylation level of global proteome as well as the enzymes in the artificial pathway, thereby decreasing yield of pinosylvin. The results revealed that the intricate balance of cellular acyl-CoA concentrations is critical for the yields of acyl-CoA-derived natural products. We next modified the enzymes in the biosynthetic pathway to adjust their acylation level and successfully improved the yield of pinosylvin. Our study uncovers the effect of protein acylation on the biosynthetic pathway, helps optimization of synthetic constructs, and provides new strategies in metabolic engineering and synthetic biology at the protein post-translational level. |
| WOS关键词 | SYNTHETIC BIOLOGY ; LYSINE ACETYLATION ; STRUCTURAL BASIS ; GENE-EXPRESSION ; POSTTRANSLATIONAL MODIFICATION ; METABOLIC-REGULATION ; ESCHERICHIA-COLI ; MALONYLATION ; STRATEGIES ; PHENYLALANINE |
| 资助项目 | National Natural Science Foundation of China[31730004] ; National Natural Science Foundation of China[21335003] ; National Natural Science Foundation of China[21575089] ; National Natural Science Foundation of China[31670066] ; National Natural Science Foundation of China[91753203] ; China Postdoctoral Science Foundation[2017M621567] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000432900600013 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279774]  |
| 专题 | 化学蛋白质组学研究中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Tan, Minjia; Ye, Bang-Ce |
| 作者单位 | 1.Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China; 2.East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xu, Jun-Yu,Xu, Ya,Chu, Xiaohe,et al. Protein Acylation Affects the Artificial Biosynthetic Pathway for Pinosylvin Production in Engineered E. coli[J]. ACS CHEMICAL BIOLOGY,2018,13(5):1200-1208. |
| APA | Xu, Jun-Yu,Xu, Ya,Chu, Xiaohe,Tan, Minjia,&Ye, Bang-Ce.(2018).Protein Acylation Affects the Artificial Biosynthetic Pathway for Pinosylvin Production in Engineered E. coli.ACS CHEMICAL BIOLOGY,13(5),1200-1208. |
| MLA | Xu, Jun-Yu,et al."Protein Acylation Affects the Artificial Biosynthetic Pathway for Pinosylvin Production in Engineered E. coli".ACS CHEMICAL BIOLOGY 13.5(2018):1200-1208. |
入库方式： OAI收割
来源：上海药物研究所
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