文献类型：期刊文献

英文题名：Improve the Biosynthesis of Baicalein and Scutellarein via Manufacturing Self-Assembly Enzyme Reactor In Vivo

作者：Ji, Dongni[1,2];Li, Jianhua[2];Xu, Fanglin[2,3,4];Ren, Yuhong[1];Wang, Yong[2,3,5]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, CAS Key Lab Synthet Biol, Shanghai 200032, Peoples R China;[3]Univ Chinese Acad Sci, Beijing 100039, Peoples R China;[4]Henan Univ, Key Lab Plant Stress Biol, Kaifeng 475004, Peoples R China;[5]Hunan Univ Med, Hunan Prov Key Lab Synthet Biol Tradit Chinese Me, Huaihua 418000, Peoples R China

年份：2021

卷号：10

期号：5

起止页码：1087

外文期刊名：ACS SYNTHETIC BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000656057600018)】；

基金：This work was funded by the National Key R&D Program of China (2018YFA0900600), the Program of Shanghai Academic Research Leader (20XD1404400), the National Natural Science Foundation of China (Grant Nos. 21778018, 31670099, 31700261, 41876084) and Research Program of State Key Laboratory of Bioreactor Engineering, the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-KJGG-002-15), the Strategic Priority Research Program `Molecular mechanism of Plant Growth and Development' of CAS (XDB27020202), the Construction of the Registry and Database of Bioparts for Synthetic Biology of the Chinese Academy of Science (No. ZSYS-016), the International Partnership Program of Chinese Academy of Science (No. 153D31KYSB20170121) and the National Key Laboratory of Plant Molecular Genetics, SIPPE, CAS.

语种：英文

外文关键词：self-assembly; baicalein; scutellarein; de novo synthesis; synthetic biology

摘要：Baicalein and scutellarein are bioactive flavonoids isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi; however, there is a lack of effective strategies for producing baicalein and scutellarein. In this study, we developed a sequential self-assembly enzyme reactor involving two enzymes in the baicalein pathway with a pair of protein-peptide interactions in E. coli. These domains enabled us to optimize the stoichiometry of two baicalein biosynthetic enzymes recruited to be an enzymes complex. This strategy reduces the accumulation of intermediates and removes the pathway bottleneck. With this strategy, we successfully promoted the titer of baicalein by 6.6-fold (from 21.6 to 143.5 mg/L) and that of scutellarein by 1.4-fold (from 84.3 to 120.4 mg/L) in a flask fermentation, respectively. Furthermore, we first achieved the de novo biosynthesis of baicalein directly from glucose, and the strain was capable of producing 214.1 mg/L baicalein by fed-batch fermentation. This work provides novel insights for future optimization and large-scale fermentation of baicalein and scutellarein.