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利用代谢工程改造酿酒酵母从葡萄糖生产红景天苷。

Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Salidroside from Glucose.

机构信息

College of Biotechnology, The State Key Laboratory of Bioreactor Engineering , East China University of Science and Technology , Shanghai 200237 , China.

Tianjin Institute of Industrial Biotechnology , Chinese Academy of Sciences , Tianjin 300308 , China.

出版信息

J Agric Food Chem. 2018 May 2;66(17):4431-4438. doi: 10.1021/acs.jafc.8b01272. Epub 2018 Apr 24.

DOI:10.1021/acs.jafc.8b01272
PMID:29671328
Abstract

Salidroside is an important plant-derived aromatic compound with diverse biological properties. Because of inadequate natural resources, the supply of salidroside is currently limited. In this work, we engineered the production of salidroside in yeast. First, the aromatic aldehyde synthase (AAS) from Petroselinum crispum was overexpressed in Saccharomyces cerevisiae when combined with endogenous Ehrlich pathway to produce tyrosol from tyrosine. Glucosyltransferases from different resources were tested for ideal production of salidroside in the yeast. Metabolic flux was enhanced toward tyrosine biosynthesis by overexpressing pathway genes and eliminating feedback inhibition. The pathway genes were integrated into yeast chromosome, leading to a recombinant strain that produced 239.5 mg/L salidroside and 965.4 mg/L tyrosol. The production of salidroside and tyrosol reached up to 732.5 and 1394.6 mg/L, respectively, by fed-batch fermentation. Our work provides an alternative way for industrial large-scale production of salidroside and tyrosol from S. cerevisiae.

摘要

红景天苷是一种具有多种生物特性的重要植物衍生芳香族化合物。由于自然资源不足,红景天苷的供应目前受到限制。在这项工作中,我们通过工程改造在酵母中生产红景天苷。首先,当与内源性 Ehrlich 途径结合时,过量表达来自皱叶欧芹的芳香醛合酶 (AAS),以从酪氨酸生产酪醇。来自不同资源的糖基转移酶被测试用于在酵母中理想地生产红景天苷。通过过表达途径基因和消除反馈抑制来增强酪氨酸生物合成的代谢通量。途径基因被整合到酵母染色体中,导致产生 239.5mg/L 红景天苷和 965.4mg/L 酪醇的重组菌株。通过分批补料发酵,红景天苷和酪醇的产量分别达到 732.5 和 1394.6mg/L。我们的工作为从酿酒酵母工业大规模生产红景天苷和酪醇提供了一种替代方法。

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