Engineering 4-coumaroyl-CoA derived polyketide production in Yarrowia lipolytica through a β-oxidation mediated strategy.

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ID: 67581
2019
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Abstract
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.
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palmer2019engineeringmetabolic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Palmer, Claire M;Miller, Kelly K;Nguyen, Ankim;Alper, Hal S;
Journal metabolic engineering
Year 2019
DOI
S1096-7176(19)30320-9
URL
Keywords
resveratrol yarrowia lipolytica curcumin metabolic engineering naringenin polyketide synthase triacetic acid lactone

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