Improve the Biosynthesis of Baicalein and Scutellarein via Manufacturing Self-Assembly Enzyme Reactor In Vivo,ACS Synthetic Biology

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Improve the Biosynthesis of Baicalein and Scutellarein via Manufacturing Self-Assembly Enzyme Reactor In Vivo
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2021-04-21 , DOI: 10.1021/acssynbio.0c00606
Dongni Ji _{1,

2} , Jianhua Li ₂ , Fanglin Xu _{2,

3,

4} , Yuhong Ren ₁ , Yong Wang _{2,

3,

5}

Affiliation

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.

中文翻译：

通过在体内制造自组装酶反应器提高黄芩素和黄芩素的生物合成

黄芩素和黄芩素是从中药黄芩中分离得到的生物活性黄酮类化合物；然而，缺乏生产黄芩素和黄芩素的有效策略。在这项研究中，我们开发了一种顺序自组装酶反应器，其中涉及黄芩素途径中的两种酶和大肠杆菌中的一对蛋白质-肽相互作用. 这些域使我们能够优化被招募为酶复合物的两种黄芩素生物合成酶的化学计量。该策略减少了中间体的积累并消除了途径瓶颈。通过这种策略，我们成功地将黄芩素的滴度分别提高了 6.6 倍（从 21.6 到 143.5 毫克/升），将黄芩素的滴度提高了 1.4 倍（从 84.3 到 120.4 毫克/升）。此外，我们首先实现了直接从葡萄糖中从头生物合成黄芩素，该菌株通过补料分批发酵能够生产214.1 mg/L的黄芩素。这项工作为黄芩素和黄芩素的未来优化和大规模发酵提供了新的见解。

更新日期：2021-05-22

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