The sesquiterpene (−)-α-bisabolol has been shown to have antibacterial, antiseptic, and anti-inflammatory activities, as well as skin-soothing properties, which has led to its wide use in cosmetics. However, the current production of (−)-α-bisabolol via steam-distillation of plants is not sustainable and cannot meet the increasing market demand. In the present study, a sustainable strategy for (−)-α-bisabolol production was developed by constructing a Yarrowia lipolytica cell factory. The oleaginous yeast Y. lipolytica has a native mevalonate pathway and strong acetyl-CoA flux, which can supply adequate precursors for (−)-α-bisabolol production. The endogenous mevalonate pathway and heterologous (−)-α-bisabolol synthesis pathway were optimized by strengthening the rate-limiting enzymes, downregulating competing pathway, as well as balancing the distribution of the common precursor acetyl-CoA between endogenous lipids and heterologous (−)-α-bisabolol synthesis by strengthening the β-oxidation pathway. Finally, (−)-α-bisabolol production of up to 364.23 mg L⁻¹ was achieved in batch culture. This sustainable method has potential for industrial (−)-α-bisabolol production.

中文翻译：

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工程化解脂耶氏酵母（Yarrowia lipolytica），用于可持续生产洋甘菊倍半萜（-）-α-bisabolol

倍半萜烯（-）-α-bisabolol具有抗菌，防腐和抗炎的作用，并具有舒缓皮肤的特性，因此已广泛用于化妆品中。然而，当前通过植物的蒸汽蒸馏生产（-）-α-双萘酚是不可持续的，不能满足日益增长的市场需求。在本研究中，通过建设解脂耶氏酵母细胞工厂，开发了一种可持续的（-）-α-双萘酚生产策略。产油酵母解脂耶氏酵母具有天然的甲羟戊酸途径和强大的乙酰辅酶A助熔剂，可为（-）-α-双萘酚的生产提供充足的前体。内源甲羟戊酸途径和异源（-）-α-bisabolol合成途径通过增强限速酶，下调竞争途径以及平衡内源性脂质和异源（-）之间常见的前体乙酰辅酶A的分布进行了优化。通过增强β-氧化途径合成-α-bisabolol。最终，在分批培养中实现了高达364.23 mg L ^-1的（-）-α-bisabolol生产。这种可持续的方法具有工业（-）-α-双萘酚的生产潜力。