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在工程大肠杆菌中从头生物合成乙酸酪醇和乙酸羟基酪醇从葡萄糖。

De novo biosynthesis of tyrosol acetate and hydroxytyrosol acetate from glucose in engineered Escherichia coli.

机构信息

Key Laboratory of Organo-Pharmaceutical Chemistry, Jiangxi Province, Gannan Normal University, Ganzhou, 341000, China.

Key Laboratory of Organo-Pharmaceutical Chemistry, Jiangxi Province, Gannan Normal University, Ganzhou, 341000, China.

出版信息

Enzyme Microb Technol. 2021 Oct;150:109886. doi: 10.1016/j.enzmictec.2021.109886. Epub 2021 Aug 19.

DOI:10.1016/j.enzmictec.2021.109886
PMID:34489039
Abstract

Tyrosol and hydroxytyrosol derived from virgin olive oil and olives extract, have wide applications both as functional food components and as nutraceuticals. However, they have low bioavailability due to their low absorption and high metabolism in human liver and small intestine. Acetylation of tyrosol and hydroxytyrosol can effectively improve their bioavailability and thus increase their potential use in the food and cosmeceutical industries. There is no report on the bioproductin of tyrosol acetate and hydroxytyrosol acetate so far. Thus, it is of great significance to develop microbial cell factories for achieving tyrosol acetate or hydroxytyrosol acetate biosynthesis. In this study, a de novo biosynthetic pathway for the production of tyrosol acetate and hydroxytyrosol acetate was constructed in Escherichia coli. First, an engineered E. coli that allows production of tyrosol from simple carbon sources was established. Four aldehyde reductases were compared, and it was found that yeaE is the best aldehyde reductase for tyrosol accumulation. Subsequently, the pathway was extended for tyrosol acetate production by further overexpression of alcohol acetyltransferase ATF1 for the conversion of tyrosol to tyrosol acetate. Finally, the pathway was further extended for hydroxytyrosol acetate production by overexpression of 4-hydroxyphenylacetate 3-hydroxylase HpaBC.

摘要

来源于初榨橄榄油和橄榄提取物的酪醇和羟基酪醇,作为功能性食品成分和营养保健品具有广泛的应用。然而,由于它们在人体肝脏和小肠中的吸收率低和代谢率高,生物利用度较低。酪醇和羟基酪醇的乙酰化可以有效地提高它们的生物利用度,从而增加它们在食品和化妆品行业的潜在用途。到目前为止,还没有关于酪醇乙酸酯和羟基酪醇乙酸酯的生物制品的报道。因此,开发微生物细胞工厂来实现酪醇乙酸酯或羟基酪醇乙酸酯的生物合成具有重要意义。在本研究中,在大肠杆菌中构建了用于生产酪醇乙酸酯和羟基酪醇乙酸酯的从头生物合成途径。首先,构建了一种能够从简单碳源生产酪醇的工程大肠杆菌。比较了四种醛还原酶,发现 yeaE 是用于酪醇积累的最佳醛还原酶。随后,通过进一步过表达醇乙酰转移酶 ATF1 将酪醇转化为酪醇乙酸酯,扩展了该途径用于生产酪醇乙酸酯。最后,通过过表达 4-羟基苯乙酸 3-羟化酶 HpaBC,进一步扩展了该途径用于生产羟基酪醇乙酸酯。

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