文献类型：期刊文献

英文题名：Engineering Saccharomyces cerevisiae for Hyperproduction of β-Amyrin by Mitigating the Inhibition Effect of Squalene on β-Amyrin Synthase

作者：Du, Meng-Meng[1];Zhu, Zhan-Tao[1];Zhang, Ge-Ge[1];Zhao, Yun-Qiu[1];Gao, Bei[1];Tao, Xin-Yi[1];Liu, Min[1];Ren, Yu-Hong[1];Wang, Feng-Qing[1];Wei, Dong-Zhi[1]

机构：[1]East China Univ Sci & Technol, Newworld Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2022

卷号：70

期号：1

起止页码：229

外文期刊名：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000763525100021)】；

基金：This work was financially supported by the National Natural Science Foundation of China (No. 21776075), the Natural Science Foundation of Shanghai (No. 20ZR1415100), and the National Key Research and Development Program of China (No. SQ2020YFC210061).

语种：英文

外文关键词：beta-amyrin; squalene; inhibition; peroxisome compartmentalization; competition pathway; Saccharomyces cerevisiae

摘要：The study aims to enhance beta-amyrin production in Saccharomyces cerevisiae by peroxisome compartmentalization. First, overaccumulated squalene was determined as a key limiting factor for the production of beta-amyrin since it could inhibit the activity of beta-amyrin synthase GgbAs1. Second, to mitigate the inhibition effect, the enhanced squalene synthesis pathway was compartmentalized into peroxisomes to insulate overaccumulated squalene from GgbAs1, and thus the specific titer of beta-amyrin reached 57.8 mg/g dry cell weight (DCW), which was 2.6-fold higher than that of the cytosol engineering strain. Third, by combining peroxisome compartmentalization with the "push-pull-restrain" strategy (ERG1 and GgbAs1 overexpression and ERG7 weakening), the production of beta-amyrin was further increased to 81.0 mg/g DCW (347.0 mg/L). Finally, through fed-batch fermentation in a 5 L fermenter, the titer of beta-amyrin reached 2.6 g/L, which is the highest reported to date. The study provides a new perspective to engineering yeasts as a platform for triterpene production.