番茄红素
毕赤酵母
代谢工程
发酵
生物技术
生物化学
食品科学
代谢途径
蛋白质工程
合成生物学
生产过剩
生物
化学
类胡萝卜素
计算生物学
基因
酶
重组DNA
作者
Xinying Zhang,Shuting Chen,Ying Lin,Wenjie Li,Denggang Wang,Shupeng Ruan,Yuxin Yang,Shuli Liang
标识
DOI:10.1021/acssynbio.3c00294
摘要
Lycopene is widely used in cosmetics, food, and nutritional supplements. Microbial production of lycopene has been intensively studied. However, few metabolic engineering studies on Pichia pastoris have been aimed at achieving high-yield lycopene production. In this study, the CRISPR/Cpf1-based gene repression system was developed and the gene editing system was optimized, which were applied to improve lycopene production successfully. In addition, the sterol regulatory element-binding protein SREBP (Sre) was used for the regulation of lipid metabolic pathways to promote lycopene overproduction in P. pastoris for the first time. The final engineered strain produced lycopene at 7.24 g/L and 75.48 mg/g DCW in fed-batch fermentation, representing the highest lycopene yield in P. pastoris reported to date. These findings provide effective strategies for extended metabolic engineering assisted by the CRISPR/Cpf1 system and new insights into metabolic engineering through transcriptional regulation of related metabolic pathways to enhance carotenoid production in P. pastoris.
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