Precise control of gene expression is critical for optimizing cellular metabolism and improving the production of valuable biochemicals. However, hard-wired approaches to pathway engineering, such as optimizing promoters, can take time and effort. Moreover, limited tools exist for controlling gene regulation in non-conventional hosts. Here, we develop a two-channel chemically-regulated gene expression system for the multi-stress tolerant yeast and use it to tune ethyl acetate production, a native metabolite produced at high titers in this yeast. To achieve this, we repurposed the plant hormone sensing modules (PYR1/HAB1 and PYR1*/HAB1*) for high dynamic-range gene activation and repression controlled by either abscisic acid (ABA) or mandipropamid (mandi). To redirect metabolic flux towards ethyl acetate biosynthesis, we simultaneously repress pyruvate dehydrogenase () and activate pyruvate decarboxylase () to enhance ethyl acetate titers. Thus, we have developed new tools for chemically tuning gene expression in and that should be deployable across many non-conventional eukaryotic hosts.

中文翻译：

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将植物激素受体重新用作化学诱导基因开关，用于酵母的动态调节

基因表达的精确控制对于优化细胞代谢和提高有价值的生化物质的生产至关重要。然而，路径工程的硬连线方法，例如优化启动子，可能需要时间和精力。此外，用于控制非常规宿主基因调控的工具有限。在这里，我们为耐多重胁迫的酵母开发了一种双通道化学调节基因表达系统，并用它来调节乙酸乙酯的产生，这是一种在该酵母中以高滴度产生的天然代谢物。为了实现这一目标，我们重新调整了植物激素传感模块（PYR1/HAB1 和 PYR1*/HAB1*）的用途，以实现由脱落酸 (ABA) 或 mandipropamid (mandi) 控制的高动态范围基因激活和抑制。为了将代谢流转向乙酸乙酯生物合成，我们同时抑制丙酮酸脱氢酶 () 并激活丙酮酸脱羧酶 () 以提高乙酸乙酯滴度。因此，我们开发了用于化学调节基因表达的新工具，并且应该可以在许多非常规真核宿主中部署。