High-Level Production of Tyrosol with Noninduced Recombinant Escherichia coli by Metabolic Engineering.,Journal of Agricultural and Food Chemistry

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High-Level Production of Tyrosol with Noninduced Recombinant Escherichia coli by Metabolic Engineering.
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-04-09 , DOI: 10.1021/acs.jafc.9b07610
Wei Xu _{1,

2} , Cui Yang _{1,

2} , Yuanyuan Xia _{1,

2} , Lihua Zhang _{1,

2} , Chunxiao Liu _{1,

2} , Haiquan Yang _{1,

2} , Wei Shen _{1,

2} , Xianzhong Chen _{1,

2}

Affiliation

Tyrosol is a pharmacologically active phenolic compound widely used in the pharmaceutical and chemical industries. Microbial fermentation has potential value as an environmentally friendly approach to tyrosol production, but suffers from low tyrosol yields and the need for expensive media additives. In this study, Escherichia coli MG1655 was modified by integrating an E. coli codon-optimized version of the Saccharomyces cerevisiae phenylpyruvate decarboxylase gene, named ARO10*, into the lacI locus. The resulting strain (YMGA*) produced 0.14 mM tyrosol from 2% glucose without the need for expensive media supplements. Subsequent deletion of E. coli genes designed to eliminate competing metabolic pathways (feaB, pheA, tyrB) or undesirable gene regulation (tyrR) produced a strain (YMGA*R) that produced 3.11 mM tyrosol. Tyrosol production was then increased to 10.92 mM by increasing the ARO10* copy number to five copies (strain YMG5A*R). Finally, tyrosol production was increased to 28 mM (ca. 3.9 g/L) by optimizing fermentation conditions in a 5 L fermenter. Engineering a productive E. coli strain with high tyrosol titer from glucose using a medium that does not require added amino acids, inducer, or antibiotic provides a solid basis to produce tyrosol through microbial fermentation.

中文翻译：

通过代谢工程技术，利用非诱导重组大肠杆菌大量生产酪醇。

酪醇是一种具有药理活性的酚类化合物，广泛用于制药和化学工业。微生物发酵作为生产酪醇的环境友好方法具有潜在价值，但是其酪醇产率低且需要昂贵的培养基添加剂。在这项研究中，通过将啤酒酵母的丙酮酸苯丙酮酸脱羧酶基因（命名为ARO10 *）整合到大肠杆菌中，对MG1655进行了修饰。所得菌株（YMGA *）从2％的葡萄糖中产生0.14 mM酪醇，而无需昂贵的培养基补充剂。随后删除旨在消除竞争性代谢途径（feaB，pheA，tyrB）或不良基因调节（tyrR）的大肠杆菌基因，产生了产生3.11 mM酪醇的菌株（YMGA * R）。然后，通过将ARO10 *拷贝数增加到5个拷贝（菌株YMG5A * R），将酪醇的产量提高到10.92 mM。最后，通过优化5 L发酵罐中的发酵条件，将酪醇产量提高到28 mM（约3.9 g / L）。使用不需要添加氨基酸，诱导剂或抗生素的培养基，用葡萄糖从酪氨酸滴定度高的生产性大肠杆菌菌株提供了通过微生物发酵生产酪醇的坚实基础。

更新日期：2020-04-24

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