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利用表达 2-吡喃酮合酶的解脂耶氏酵母通过靶向基因缺失生产三醋酸内酯。

Triacetic acid lactone production using 2-pyrone synthase expressing Yarrowia lipolytica via targeted gene deletion.

机构信息

Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.

Center for Sustainable Resource Science, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.

出版信息

J Biosci Bioeng. 2023 Oct;136(4):320-326. doi: 10.1016/j.jbiosc.2023.07.006. Epub 2023 Aug 11.

Abstract

An environmentally sustainable world can be realized by using microorganisms to produce value-added materials from renewable biomass. Triacetic acid lactone (TAL) is a high-value-added compound that is used as a precursor of various organic compounds such as food additives and pharmaceuticals. In this study, we used metabolic engineering to produce TAL from glucose using an oleaginous yeast Yarrowia lipolytica. We first introduced TAL-producing gene 2-pyrone synthase into Y. lipolytica, which enabled TAL production. Next, we increased TAL production by engineering acetyl-CoA and malonyl-CoA biosynthesis pathways by redirecting carbon flux to glycolysis. Finally, we optimized the carbon and nitrogen ratios in the medium, culminating in the production of 4078 mg/L TAL. The strategy presented in this study had the potential to improve the titer and yield of polyketide biosynthesis.

摘要

通过利用微生物将可再生生物质转化为高附加值材料,可以实现环境可持续发展的世界。三乙酰基谷酰胺(TAL)是一种高附加值化合物,可用作食品添加剂和药物等各种有机化合物的前体。在这项研究中,我们使用代谢工程技术,利用产油酵母解脂耶氏酵母(Yarrowia lipolytica)从葡萄糖生产 TAL。我们首先将 TAL 产生基因 2-吡喃酮合酶引入 Y. lipolytica,使其能够生产 TAL。接下来,我们通过将碳通量重新导向糖酵解来工程化乙酰辅酶 A 和丙二酰辅酶 A 生物合成途径,从而提高 TAL 的产量。最后,我们优化了培养基中的碳氮比,最终 TAL 的产量达到了 4078mg/L。本研究提出的策略有可能提高聚酮生物合成的滴度和产率。

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