原材料
生物燃料
酵母
代谢工程
生化工程
化学
甲醇
生产(经济)
可再生能源
生物化学
持续性
工程类
废物管理
生物
有机化学
经济
宏观经济学
生态学
电气工程
酶
作者
Linhui Gao,Rui Hou,Peng Cai,Lun Yao,Xiaoyan Wu,Yunxia Li,Lihua Zhang,Yongjin J. Zhou
出处
期刊:JACS Au
[American Chemical Society]
日期:2024-04-29
卷期号:4 (7): 2474-2483
被引量:25
标识
DOI:10.1021/jacsau.4c00106
摘要
Microbial metabolic engineering provides a feasible approach to sustainably produce advanced biofuels and biochemicals from renewable feedstocks. Methanol is an ideal feedstock since it can be massively produced from CO2 through green energy, such as solar energy. However, engineering microbes to transform methanol and overproduce chemicals is challenging. Notably, the microbial production of isoprenoids from methanol is still rarely reported. Here, we extensively engineered Pichia pastoris (syn. Komagataella phaffii) for the overproduction of sesquiterpene α-bisabolene from sole methanol by optimizing the mevalonate pathway and peroxisomal compartmentalization. Furthermore, through label-free quantification (LFQ) proteomic analysis of the engineered strains, we identified the key bottlenecks in the peroxisomal targeting pathway, and overexpressing the limiting enzyme EfmvaE significantly improved α-bisabolene production to 212 mg/L with the peroxisomal pathway. The engineered strain LH122 with the optimized peroxisomal pathway produced 1.1 g/L α-bisabolene under fed-batch fermentation in shake flasks, achieving a 69% increase over that of the cytosolic pathway. This study provides a viable approach for overproducing isoprenoid from sole methanol in engineered yeast cell factories and shows that proteomic analysis can help optimize the organelle compartmentalized pathways to enhance chemical production.
科研通智能强力驱动
Strongly Powered by AbleSci AI