Resveratrol is a plant secondary metabolite with multiple health-beneficial properties. Microbial production of resveratrol in model microorganisms requires extensive engineering to reach commercially viable levels. Here, we explored the potential of the non-conventional yeast Yarrowia lipolytica to produce resveratrol and several other shikimate pathway-derived metabolites (p-coumaric acid, cis,cis-muconic acid, and salicylic acid). The Y. lipolytica strain expressing a heterologous pathway produced 52.1 ± 1.2 mg/L resveratrol in a small-scale cultivation. The titer increased to 409.0 ± 1.2 mg/L when the strain was further engineered with feedback-insensitive alleles of the key genes in the shikimate pathway and with five additional copies of the heterologous biosynthetic genes. In controlled fed-batch bioreactor, the strain produced 12.4 ± 0.3 g/L resveratrol, the highest reported titer to date for de novo resveratrol production, with a yield on glucose of 54.4 ± 1.6 mg/g and a productivity of 0.14 ± 0.01 g/L/h. The study showed that Y. lipolytica is an attractive host organism for the production of resveratrol and possibly other shikimate-pathway derived metabolites.

白藜芦醇是一种植物次生代谢物，具有多种有益健康的特性。模型微生物中白藜芦醇的微生物生产需要广泛的工程设计才能达到商业上可行的水平。在这里，我们探索了非常规酵母解脂耶氏酵母生产白藜芦醇和其他几种莽草酸途径衍生代谢物（对香豆酸、顺式、顺式粘康酸和水杨酸）的潜力。在解脂耶表达异源途径的菌株在小规模培养中产生 52.1 ± 1.2 mg/L 白藜芦醇。当用莽草酸途径中关键基因的反馈不敏感等位基因和异源生物合成基因的五个额外拷贝进一步改造菌株时，滴度增加到 409.0 ± 1.2 mg/L。在受控补料分批生物反应器中，该菌株生产 12.4 ± 0.3 g/L 白藜芦醇，这是迄今为止从头白藜芦醇生产中报告的最高滴度，葡萄糖产量为 54.4 ± 1.6 mg/g，生产率为 0.14 ± 0.01 g /升/小时。研究表明，解脂耶氏酵母是一种有吸引力的宿主生物，可用于生产白藜芦醇和其他莽草酸途径衍生的代谢物。