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通过在海洋真菌中嫁接异源聚酮合酶途径来优化二十碳五烯酸的生产。

Optimizing Eicosapentaenoic Acid Production by Grafting a Heterologous Polyketide Synthase Pathway in the Thraustochytrid .

机构信息

CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Energy Genetics, Shandong Engineering Laboratory of Single Cell Oil, Qingdao Engineering Laboratory of Single Cell Oil, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, Shandong, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

J Agric Food Chem. 2020 Oct 7;68(40):11253-11260. doi: 10.1021/acs.jafc.0c04299. Epub 2020 Sep 1.

DOI:10.1021/acs.jafc.0c04299
PMID:32829640
Abstract

Eicosapentaenoic acid (EPA) is an essential nutritional supplement for human health. The most prominent dietary source of EPA is fish oil, which is unsustainable because of the decline in fishery resources and serious environmental pollution. Alternatively, a heterologous polyketide synthase pathway for EPA biosynthesis was assembled in Thraustochytrid . A 2A peptide-based facile assembly platform that can achieve multigene expression as a polycistron was first established. The platform was then applied to express the EPA biosynthetic gene cluster from in . In the shake flask fermentation, the lipid and PUFA yields of the mutant were increased by 26.9 and 36.0%, respectively, and led to about 5-fold increase of the EPA yield. The final EPA titer reached 2.7 g/L in fed-batch fermentation. This study provides a novel metabolic engineering strategy to regulate the EPA ratio in microalgal oil for human nutritional supplementation.

摘要

二十碳五烯酸(EPA)是人类健康的必需营养补充剂。EPA 的最主要膳食来源是鱼油,但由于渔业资源的减少和严重的环境污染,鱼油已不可持续。另一方面,我们在海洋真菌里组装了一个 EPA 生物合成的异源聚酮合酶途径。我们首先建立了一个基于 2A 肽的简便组装平台,可实现多基因表达作为多顺反子。然后,我们将该平台应用于从 中表达 EPA 生物合成基因簇。在摇瓶发酵中,突变体的脂质和多不饱和脂肪酸(PUFA)产量分别提高了 26.9%和 36.0%,导致 EPA 产量增加了约 5 倍。在分批补料发酵中,最终 EPA 浓度达到 2.7 g/L。这项研究为调节微藻油中 EPA 比例以用于人类营养补充提供了一种新的代谢工程策略。

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