Significance: Polyketides are important molecules for both their bioactive traits and their potential as chemical building blocks. However, production of these molecules through chemistry and biocatalysts is restricted in yield and titer. Here, we demonstrate that the nonconventional yeast Yarrowia lipolytica can serve as a potent host for such production. This work provides a comprehensive evaluation of three separate pathways toward acetyl–CoA and malonyl–CoA in this host, enabling high-titer production of triacetic acid lactone. Beyond achieving unprecedented titers and appreciable yields, this production capacity allows for both purification from fermentation broth and conversion into a material using simple reaction conditions.