谷氨酸棒杆菌
大肠杆菌
枯草芽孢杆菌
发酵
化学
代谢工程
生物化学
组氨酸
生物制品
氨基酸
严格的回应
酶
生物
细菌
基因
生物技术
遗传学
生物燃料
作者
Hongxia Wu,Daoguang Tian,Xiaoguang Fan,Weiming Fan,Yue Zhang,Shuai Jiang,Chenhui Wen,Qian Ma,Ning Chen,Xixian Xie
标识
DOI:10.1021/acssynbio.0c00163
摘要
l-Histidine is a functional amino acid with numerous therapeutic and ergogenic properties. It is one of the few amino acids that is not produced on a large scale by microbial fermentation due to the lack of an efficient microbial cell factory. In this study, we demonstrated the engineering of wild-type Escherichia coli to overproduce histidine from glucose. First, removal of transcription attenuation and histidine-mediated feedback inhibition resulted in 0.8 g/L histidine accumulation. Second, chromosome-based optimization of the expression levels of histidine biosynthesis genes led to a 4.75-fold increase in histidine titer. Third, strengthening phosphoribosyl pyrophosphate supply and rerouting the purine nucleotide biosynthetic pathway improved the histidine production to 8.2 g/L. Fourth, introduction of the NADH-dependent glutamate dehydrogenase from Bacillus subtilis and the lysine exporter from Corynebacterium glutamicum enabled the final strain HW6-3 to produce 11.8 g/L histidine. Finally, 66.5 g/L histidine was produced under fed-batch fermentation, with a yield of 0.23 g/g glucose and a productivity of 1.5 g/L/h. This is the highest titer and productivity of histidine ever reported from an engineered strain. Additionally, the metabolic strategies utilized here can be applied to engineering other microorganisms for the industrial production of histidine and related bioproducts.
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