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微生物合成没食子酸及其糖苷β-葡萄糖没食子苷。

Microbial synthesis of gallic acid and its glucoside β-glucogallin.

机构信息

State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China.

出版信息

Biotechnol Bioeng. 2024 Nov;121(11):3527-3536. doi: 10.1002/bit.28820. Epub 2024 Jul 30.

Abstract

Gallic acid (GA) and β-glucogallin (BGG) are natural products with diverse uses in pharmaceutical, food, chemical and cosmetic industries. They are valued for their wide-ranging properties such as antioxidant, antibacterial, antidiabetic, and anticancer properties. Despite their significant importance, microbial production of GA and BGG faces challenges such as limited titers and yields, along with the incomplete understanding of BGG biosynthesis pathways in microorganisms. To address these challenges, we developed a recombinant Escherichia coli strain capable of efficiently producing GA. Our approach involved screening efficient pathway enzymes, integrating biosynthetic pathway genes into the genome while balancing carbon flux via adjusting expression levels, and strengthening the shikimate pathway to remove bottlenecks. The resultant strain achieved impressive results, producing 51.57 g/L of GA with a carbon yield of 0.45 g/g glucose and a productivity of 1.07 g/L/h. Furthermore, we extended this microbial platform to biosynthesize BGG by screening GA 1-O-glucosyltransferase, leading to the de novo production of 92.42 mg/L of BGG. This work establishes an efficient chassis for producing GA at an industrial level and provides a microbial platform for generating GA derivatives.

摘要

没食子酸(GA)和β-葡萄糖没食子苷(BGG)是具有多种用途的天然产物,广泛应用于制药、食品、化工和化妆品行业。它们具有抗氧化、抗菌、抗糖尿病和抗癌等多种特性,因此具有很高的价值。尽管它们非常重要,但 GA 和 BGG 的微生物生产面临着一些挑战,例如产量和浓度有限,以及对微生物中 BGG 生物合成途径的不完全了解。为了解决这些挑战,我们开发了一种能够高效生产 GA 的重组大肠杆菌菌株。我们的方法包括筛选高效的途径酶,将生物合成途径基因整合到基因组中,同时通过调整表达水平平衡碳通量,并加强莽草酸途径以消除瓶颈。结果表明,该菌株生产了 51.57 g/L 的 GA,碳得率为 0.45 g/g 葡萄糖,生产强度为 1.07 g/L/h。此外,我们通过筛选 GA 1-O-葡萄糖基转移酶,将这个微生物平台扩展到 BGG 的生物合成,从而实现了 92.42 mg/L 的 BGG 的从头合成。这项工作为在工业水平上生产 GA 建立了一个高效的底盘,并为生成 GA 衍生物提供了一个微生物平台。

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