文献类型：期刊文献

英文题名：Omics-guided global rewiring of yeast metabolism enables high-level production of β-lactoglobulin

作者：Yao, Chaoying[1];Zhu, Hong[2];An, Qi[2];Zhang, Meng[2];Zheng, Yitao[1];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]Shanghai Angecon Biotechnol Co Ltd, Shanghai 201318, Peoples R China;[3]Shanghai Collaborat Innovat Ctr Biomfg, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2026

卷号：82

外文期刊名：FOOD BIOSCIENCE

收录：;Scopus(收录号：2-s2.0-105043341493);WOS:【SCI-EXPANDED(收录号:WOS:001816152900001)】；

基金：This work was supported by the Shanghai Explorer Program (24TS1411600) , and Shanghai Agricultural Science and Technology Innovation Project (K2025017) .

语种：英文

外文关键词：Komagataella phaffii; beta-lactoglobulin; Precision fermentation; Multi-omics

摘要：beta-Lactoglobulin ((3-LG), the major natural whey protein from milk, is an important food protein with broad nutritional and functional value and has recently emerged as an attractive target for microbial recombinant expression and precision fermentation. However, the host factors that limit its high-level production are still not well understood. In this study, we evaluated different systems of the industrial yeast Komagataella phaffii for (3-LG expression and established an efficient methanol-free (3-LG recombinant production platform based on this host. Integrated transcriptomic and metabolomic analysis revealed the key bottlenecks in high-level (3-LG production. The key host determinants of (3-LG production involved multiple modules, including energy supply, tricarboxylic acid (TCA)-linked carbon and nitrogen metabolism, amino acid metabolism, redox homeostasis, and protein folding and secretion. Guided by this systems-level mapping, ATP5, GDH3, IDH1 and PPI1 were identified as key targets for further engineering. Combinatorial rewiring of these targets together with amino acid feeding allowed a remarkable production improvement of (3-LG, resulting in a final titer of 13.88 g/L in bioreactor fermentation. To our knowledge, this is the reported highest titer for heterologous (3-LG expression in yeast so far. Overall, this study provides a robust and scalable microbial chassis for sustainable dairy protein production and demonstrates the potential of multi-omics strategies for establishing food protein cell factories.