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Graphical Abstract and Lay SummaryEfficient production of ??ionone holds great promise for the flavor and fragrance industry. However, traditional extraction methods are limited by low yields and high costs. In this study, we established a robust Yarrowia lipolytica cell factory via a systematic metabolic engineering strategy. First, a high ??carotene?producing strain was constructed by strengthening the MVA pathway and attenuating squalene synthesis. Subsequently, the PhCCD1 gene and the isoprenol utilization pathway (IUP) were introduced to enable ??ionone synthesis and enhance precursor supply. Finally, high?titer production was achieved via fed?batch fermentation in a 5?L bioreactor.ABSTRACT??Ionone, prized for its characteristic violet aroma and woody undertones, has emerged as a valuable ingredient in the fragrance industry. Beyond its aromatic qualities, growing interest in its diverse biological activities has positioned it as a compound of relevance in the biopharmaceutical field. As production strategies shift from traditional chemical synthesis toward more sustainable biological routes, this study explores the engineered biosynthesis of ??ionone in Yarrowia lipolytica. Through systematic combinatorial metabolic engineering, a strain capable of accumulating 743 mg/L of ??carotene was constructed. Heterologous expression of the petunia?derived carotenoid cleavage dioxygenase gene PhCCD1 enabled efficient conversion of ??carotene to ??ionone, yielding 137 mg/L in shake?flask cultures. Subsequent integration of the isoprene alcohol metabolic pathway further enhanced precursor supply, boosting ??ionone production to 236.7 mg/L in shake flasks. In a 5 L bioreactor, optimization of the culture medium and feeding strategy led to a final titer of 624.7 mg/L. Collectively, these results establish a promising and replicable strategy for developing microbial cell factories capable of efficient ??ionone synthesis.