文献类型：期刊文献

英文题名：Programmable and controllable sexual life cycle for improved evolution in Komegataella phaffii

作者：Song, Lili[1];Wu, Yanyan[1];Hua, Li[1];Liu, Qi[1];Li, Yunhao[1];Zhou, Xiangshan[2];Cai, Menghao[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]China Resources Biopharmaceut Co Ltd, Shenzhen 518132, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2026

卷号：97

外文期刊名：METABOLIC ENGINEERING

收录：;EI(收录号：20262721025771);WOS:【SCI-EXPANDED(收录号:WOS:001815609800001)】；

基金：Funding This research was supported by the Shanghai Explorer Program (24TS1411600) , National Key R & D Program of China (2022YFC2805102) , and Shanghai Agricultural Science and Technology Innovation Project (K2025017) .

语种：英文

外文关键词：Cell proliferation - Life cycle

摘要：The sexual life cycle represents a natural engine for promoting genetic diversity in yeast. However, harnessing it for controllable, rapid evolution in industrial yeast strains remains a big challenge. Here, we developed quantitative mating and sporulation methods for an industrial yeast Komagataella phaffii. Functional genes for its sexual life cycle were identified, and deficiency of key sporulation targets generated stable diploids with enhanced stress tolerance and recombinant protein production. A fully programmable life-cycle system was constructed, for which mating and sporulation are orthogonally controlled by different inducible signals. Leveraging this system, we developed an in situ mating-sporulation shift (iMASS) platform in liquid culture. Applications of iMASS under diverse selection pressures accelerated cell evolution, generating strains with improved robustness and protein productions. Our work proposes a paradigm that integrates rational design with controlled sexual reproduction for directed microbial evolution.