文献类型：期刊文献

英文题名：A programmable high-expression yeast platform responsive to user-defined signals

作者：Liu, Qi[1];Song, Lili[1];Peng, Qiangqiang[1];Zhu, Qiaoyun[1];Shi, Xiaona[1];Xu, Mingqiang[1];Wang, Qiyao[1];Zhang, Yuanxing[1,2];Cai, Menghao[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Collaborat Innovat Ctr Biomfg, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：8

期号：6

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20220711646780);WOS:【SCI-EXPANDED(收录号:WOS:000757383500010)】；

基金：This work was funded by the National Natural Science Foundation of China (31870073), National Key R&D Program of China (2018YFC1706200, 2020YFA0907800), Shanghai Rising-Star Program, China (19QA1402700), and the Fundamental Research Funds for Central Universities (2222012016019).

语种：英文

外文关键词：Recombinant proteins - Transcription

摘要：Rapidly growing yeasts with appropriate posttranslational modifications are favored hosts for protein production in the biopharmaceutical industry. However, limited production capacity and intricate transcription regulation restrict their application and adaptability. Here, we describe a programmable high-expression yeast platform, SynPic-X, which responds to defined signals and is broadly applicable. We demonstrated that a synthetic improved transcriptional signal amplification device (iTSAD) with a bacterial-yeast transactivator and bacterial-yeast promoter markedly increased expression capacity in Pichia pastoris. CRISPR activation and interference devices were designed to strictly regulate iTSAD in response to defined signals. Engineered switches were then constructed to exemplify the response of SynPic-X to exogenous signals. Expression of alpha-amylase by SynPic-R, a specific SynPic-X, in a bioreactor proved a methanol-free high-production process of recombinant protein. Our SynPic-X platform provides opportunities for protein production in customizable yeast hosts with high expression and regulatory flexibility.