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通过异源表达线粒体转运蛋白 MTT 提高解脂耶氏酵母中的衣康酸产量。

Enhanced itaconic acid production in Yarrowia lipolytica via heterologous expression of a mitochondrial transporter MTT.

机构信息

Shandong Provincial Key Laboratory of Food and Fermentation Engineering, Shandong Food Ferment Industry Research & Design Institute, Qilu University of Technology (Shandong Academy of Sciences), No.41 Jiefang road, Jinan, 250013, People's Republic of China.

State Key Laboratory of Microbial Technology, Shandong University, 266237, Qingdao, People's Republic of China.

出版信息

Appl Microbiol Biotechnol. 2019 Mar;103(5):2181-2192. doi: 10.1007/s00253-019-09627-z. Epub 2019 Jan 18.

DOI:10.1007/s00253-019-09627-z
PMID:30656392
Abstract

Itaconic acid, a promising platform chemical, has been applied in many fields of industrial production. As a potential candidate for itaconic acid production, Yarrowia lipolytica possesses several innate abilities such as the tolerance of low-pH and high-shear stress, fast growth rate, cultivation flexibility, and easy for genetic manipulation. Here, Y. lipolytica Po1f which was tested to show high tolerance to itaconic acid could accumulate itaconic acid (0.363 g/L) by expressing the Aspergillus terreus cis-aconitic acid decarboxylase (CAD). Then, we tried to improve the supply and transport of the immediate precursor cis-aconitic acid by overexpressing a series of genes; these results indicate that overexpression of mitochondrial cis-aconitate transporter MTT is beneficial to the itaconic acid biosynthesis in Y. lipolytica. Further culture optimization enabled 22.03 g/L of itaconic acid to be produced in bioreactors, about 60-fold improvement over the initial titer, which is the highest itaconic acid production achieved at low pH by yeast reported worldwide, to data. This study demonstrates the great potential of Y. lipolytica as an industrial platform for itaconic acid production.

摘要

衣康酸是一种很有前途的平台化学品,已被应用于许多工业生产领域。解脂耶氏酵母作为衣康酸生产的潜在候选者,具有耐低 pH 值和高剪切力、生长速度快、培养灵活性强、易于遗传操作等固有能力。在这里,经过测试显示对衣康酸具有高耐受性的 Y. lipolytica Po1f 通过表达 Aspergillus terreus cis-aconitic acid decarboxylase (CAD) 可以积累衣康酸(0.363 g/L)。然后,我们试图通过过表达一系列基因来提高直接前体顺乌头酸的供应和运输;这些结果表明,过表达线粒体顺乌头酸转运蛋白 MTT 有利于 Y. lipolytica 中的衣康酸生物合成。进一步的培养优化使生物反应器中能够生产 22.03 g/L 的衣康酸,比初始滴度提高了约 60 倍,这是迄今为止报道的酵母在低 pH 值下生产衣康酸的最高产量。本研究表明,解脂耶氏酵母作为衣康酸生产的工业平台具有巨大的潜力。

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