(−)-α-Bisabolol exhibits analgesic, anti-inflammatory, and skin-soothing properties and is widely applied in the cosmetic and pharmaceutical industries. The use of plant essential oil distillation or chemical synthesis to produce (−)-α-bisabolol is both inefficient and unsustainable. Currently, the microbial production of (−)-α-bisabolol mainly relies on Escherichia coli and Saccharomyces cerevisiae as chassis strains; however, high concentrations of (−)-α-bisabolol have certain toxicity to the strain. This study uses synthetic biology and metabolic engineering strategies to redesign a solvent-tolerant Serratia marcescens for the efficient production of (−)-α-bisabolol. By introducing the Haloarchaea-type mevalonate (MVA) pathway and the (−)-α-bisabolol biosynthesis pathway, we successfully constructed a strain capable of producing (−)-α-bisabolol. The coexpression of the chaperone protein DnaK/J significantly enhanced the soluble expression of the (−)-α-bisabolol synthase, resulting in a 10% increase in (−)-α-bisabolol titer. Furthermore, knockout of the PhoA gene, which reduced the formation of the byproduct farnesol (FOH), further increased the (−)-α-bisabolol titer to 3.21 g/L. In a 5 L bioreactor, S. marcescens achieved a final (−)-α-bisabolol titer of 30.2 g/L, representing the highest titer reported to date. This research provides guidance for the production of (−)-α-bisabolol in nonmodel microorganisms without the requirement for induction.

中文翻译：

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基于外源性盐古菌 MVA 途径和内源性分子伴侣构建用于 （−）-α-红没药醇生产的高产粘质沙雷氏菌


（−）-α-红没药醇具有镇痛、抗炎和舒缓皮肤的特性，广泛应用于化妆品和制药行业。使用植物精油蒸馏或化学合成来生产 （-）-α-红没药醇既低效又不可持续。目前，（−）-α-红没药醇的微生物生产主要依赖于大肠杆菌和酿酒酵母作为底盘菌株;然而，高浓度的 （-）-α-红没药醇对菌株有一定的毒性。本研究使用合成生物学和代谢工程策略重新设计耐溶剂的粘质沙雷氏菌，以高效生产 （-）-α-红没药醇。通过引入盐古细菌型甲羟戊酸酯 （MVA） 途径和 （−）-α-红没药醇生物合成途径，我们成功构建了能够产生 （−）-α-红没药醇的菌株。伴侣蛋白 DnaK/J 的共表达显着增强了 （-）-α-红没药醇合酶的可溶性表达，导致 （-）-α-红没药醇滴度增加 10%。此外，敲除 PhoA 基因减少了副产物法呢醇 （FOH） 的形成，进一步将 （−）-α-红没药醇滴度提高至 3.21 g/L。在 5 L 生物反应器中，粘质链球菌的最终 （−）-α-红没药醇滴定度为 30.2 g/L，这是迄今为止报道的最高滴度。本研究为在非模式微生物中生产 （-）-α-红没药醇提供了指导，而无需诱导。