Polyketides are a diverse class of molecules sought after for their valuable properties, including as potential pharmaceuticals. Previously, we demonstrated that the oleaginous yeast Yarrowia lipolytica is an optimal host for production of the simple polyketide, triacetic acid lactone (TAL). We here expand the capacities of this host by overcoming previous media challenges and enabling production of more complex polyketides. Specifically, we employ a β-oxidation related strategy to improve polyketide production directly from defined media. Beyond TAL production, we establish biosynthesis of the 4-coumaroyl-CoA derived polyketides: naringenin, resveratrol, and bisdemethoxycurcumin, as well as the diketide intermediate, (E)-5-(4-hydroxyphenyl)-3-oxopent-4-enoic acid. In this background, we enable high-level de novo production of naringenin through import of both a heterologous pathway and a mutant Y. lipolytica allele. In doing so, we generated an averaged maximum titer of 898 mg/L naringenin, the highest titer reported to date in any host. These results demonstrate that Y. lipolytica is an ideal polyketide production host for more complex 4-coumaroyl-CoA derived products.

聚酮化合物是一类因其有价值的性质而寻求的分子，包括作为潜在的药物。以前，我们证明油质酵母解脂耶氏酵母是生产简单聚酮化合物三乙酸内酯（TAL）的最佳宿主。我们在这里通过克服以前的媒体挑战并能够生产更复杂的聚酮化合物来扩展该宿主的能力。具体而言，我们采用与β氧化有关的策略来直接从定义的培养基中改善聚酮化合物的生产。除了生产TAL以外，我们还建立了4香豆酰基辅酶A衍生的聚酮化合物的生物合成：柚皮素，白藜芦醇和双去甲氧基姜黄素，以及双酮化合物中间体（E）-5-（4-羟苯基）-3-氧opent-4-烯酸。在这种背景下，我们可以通过导入异源途径和突变解脂耶氏酵母等位基因，来从头生产柚皮苷。这样，我们产生的平均最大滴度为898 mg / L柚皮素，是迄今为止报道的任何宿主中最高的滴度。这些结果表明解脂耶氏酵母是用于更复杂的4-香豆酰基-CoA衍生产品的理想聚酮化合物生产宿主。