代谢工程大肠杆菌从葡萄糖高效生产1-组氨酸。,ACS Synthetic Biology

当前位置： X-MOL 学术 › ACS Synth. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

代谢工程大肠杆菌从葡萄糖高效生产1-组氨酸。
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-05-29 , DOI: 10.1021/acssynbio.0c00163
Heyun Wu _{1,

2} , Daoguang Tian _{1,

2} , Xiaoguang Fan _{1,

2} , Weiming Fan ₃ , Yue Zhang _{1,

2} , Shuai Jiang _{1,

2} , Chenhui Wen _{1,

2} , Qian Ma _{1,

2} , Ning Chen _{1,

2} , Xixian Xie _{1,

2}

Affiliation

1-组氨酸是一种具有许多治疗和致敏特性的功能性氨基酸。它是由于缺乏有效的微生物细胞工厂而无法通过微生物发酵大规模生产的少数氨基酸之一。在这项研究中，我们证明了野生型大肠杆菌的工程化从葡萄糖中过量生产组氨酸。首先，去除转录减弱和组氨酸介导的反馈抑制导致0.8 g / L组氨酸的积累。第二，基于染色体的组氨酸生物合成基因表达水平的优化导致组氨酸滴度提高了4.75倍。第三，加强磷酸核糖焦磷酸的供应并重新路由嘌呤核苷酸的生物合成途径，可将组氨酸产量提高到8.2 g / L。第四，引入枯草芽孢杆菌的NADH依赖性谷氨酸脱氢酶和谷氨酸棒杆菌的赖氨酸出口。使最终菌株HW6-3产生11.8 g / L组氨酸。最后，在分批补料发酵中产生了66.5g / L的组氨酸，葡萄糖的产量为0.23g / g，生产率为1.5g / L / h。这是工程菌株迄今报道的最高的组氨酸滴度和生产率。另外，这里使用的代谢策略可以应用于工程改造其他微生物，以工业生产组氨酸和相关生物产品。

"点击查看英文标题和摘要"

Highly Efficient Production of l-Histidine from Glucose by Metabolically Engineered Escherichia coli.

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.

更新日期：2020-07-17

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南