Advances in Polyketide Related Biosynthesis Using Engineered Yarrowia lipolytica
TL;DR
This review summarizes recent progress in PKS pathway engineering in Y. lipolytica, covering the biosynthesis and optimization of representative type I and type III polyketides, including 6-MSA, TAL and the unnatural polyketide HHEP.
Abstract
Yarrowia lipolytica , a robust oleaginous non-conventional yeast, exhibits unique advantages for natural product biosynthesis due to its high endogenous acetyl-CoA and malonyl-CoA fluxes, broad substrate tolerance, mature genetic tools and superior biosafety. Polyketides, synthesized by polyketide synthases (PKSs), are structurally diverse high-value compounds with extensive pharmaceutical and industrial applications. Attributing to its inherent lipid metabolism, Y. lipolytica serves as a superior chassis for polyketide synthesis compared with traditional yeast and bacterial hosts. This review summarizes recent progress in PKS pathway engineering in Y. lipolytica , covering the biosynthesis and optimization of representative type I and type III polyketides, including 6-MSA, TAL and the unnatural polyketide HHEP. The metabolic engineering strategies for PKS-derived phenylpropanoids, such as resveratrol and naringenin, are also discussed. Special emphasis is given to the metabolic interplay between heterologous PKS pathways and endogenous lipid metabolism, highlighting the precursor competition and flux redistribution that determine final product yields. Key challenges and prospective optimization strategies are also discussed to facilitate future development of robust Y. lipolytica cell factories for efficient polyketide bioproduction.