Biological-chemical method for synthesizing p-menthane-3,8-diol

The cyclic monoterpene p-menthane-3,8-diol exhibits highly effective mosquito-repellent activity. Current industrial production of PMD depends on chemically synthesized citronellal as a precursor. To provide a green, sustainable alternative for citronellal supply, we engineered a Saccharomyces cerevisiae strain for efficient de novo biosynthesis of citronellal. By enhancing geraniol synthesis, systematically redesigning the endogenous oxidoreductase system, and implementing metabolic optimization strategies, a citronellal titer of 0.13 g/L was achieved in shake-flask cultivation. By integrating this microbial fermentation step with subsequent chemical catalysis, we established a biological-chemical method for PMD production, achieving a final PMD yield of 0.64 g/L. This work represents the first semisynthetic route from glucose to PMD via a biological-chemical method, offering a novel and sustainable paradigm for PMD manufacture.