2-Phenylethanol (2-PE) is an important flavor ingredient and is widely applied in the fields of food, cosmetics, and pharmaceuticals. Despite that Saccharomyces cerevisiae has the ability to naturally synthesize 2-PE via the Ehrlich pathway, de novo synthesis of 2-PE in high titer still remains a huge challenge. In this study, a non-native styrene degradation pathway was introduced into S. cerevisiae, which represents the first time to demonstrate the functional expression of “styrene-derived” 2-PE synthesis in yeast. Using a host strain engineered with L-phenylalanine (L-Phe) overproduction, the heterologous 2-PE pathway coupled with endogenous Ehrlich pathway produced 233 mg/L 2-PE under shake flasks. Additionally, we further engineered the permease transporters to improve the intracellular L-Phe availability, and further improved the 2-PE titer to 680 mg/L. Taken together, our work represents one of the pioneering reports to explore “styrene-derived” pathway in S. cerevisiae. The synthetic yeast described here might be used as a platform for the future development of next-generation high-yielding 2-PE yeast strains.

Key Points

• A styrene-derived pathway was established in yeast for 2-phenylethanol productions; membrane-associated styrene oxide isomerase was functional in yeast.

• Transporter engineering to improve the L-phenylalanine importation with enhanced 2-phenylethanol productions.

Graphical abstract

中文翻译：

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苯乙烯衍生途径在发芽酵母中生产2-苯基乙醇的用途

2-苯乙醇（2-PE）是一种重要的风味成分，已广泛应用于食品，化妆品和药品领域。尽管酿酒酵母具有通过Ehrlich途径天然合成2-PE的能力，但在高滴度下从头合成2-PE仍然是一个巨大的挑战。在这项研究中，非天然苯乙烯降解途径被引入酿酒酵母。，这是首次证明酵母中“苯乙烯衍生的” 2-PE合成的功能性表达。使用经过过度生产的L-苯丙氨酸（L-Phe）改造的宿主菌株，异源2-PE途径与内源性Ehrlich途径偶联在摇瓶中产生233 mg / L 2-PE。此外，我们进一步设计了渗透酶转运蛋白，以提高细胞内L-Phe的利用率，并将2-PE滴度进一步提高至680 mg / L。综上所述，我们的工作代表了探索酿酒酵母中“苯乙烯衍生”途径的开创性报告之一。此处描述的合成酵母可以用作下一代高产2-PE酵母菌株未来开发的平台。

关键点

•在酵母中建立了苯乙烯衍生的途径来生产2-苯基乙醇；膜相关的苯乙烯氧化物异构酶在酵母中具有功能。

•运输工程，以提高2-苯基乙醇的产量来提高L-苯丙氨酸的进口量。

图形概要