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Metabolic engineering of the yeast Yarrowia lipolytica for the production of even- and odd-chain fatty acids

Abstract : Microbial oils are regarded as promising alternatives to fossil fuels with growing environmental and energy concerns. Odd-chain fatty acids (OCFAs), a type of unusual lipids, are value-added compounds with various biotechnological applications. The objective of the thesis was to develop Yarrowia lipolytica as a platform strain for the production of OCFAs by metabolic engineering.For developing Y. lipolytica, the identification and characterization of a new series of erythritol-hybrid-inducible promoters (pEYK1, pEYD1, and derivatives) were explored. The hybrid promoter series showed variable strengths, erythritol-based induction increased 2.2 to 32.3 times in the WT strain and 2.9 to 896.1 times in the eyk1Δ strain, which will improve the modulation of gene expression for metabolic engineering of Y. lipolytica.For OCFA production, tolerance to propionate was studied. Two genes, RTS1 and MFS1, were identified as propionate-tolerant genes by screening a genomic DNA library. Through metabolic engineering strategies, such as inhibiting competitive pathways, increasing precursor pools, and enhancement of total lipid accumulation, OCFA production was increased from 0.14 g/L to 1.87 g/L. De novo production of OCFAs without propionate supplementation was also explored by overexpression of the threonine synthesis pathway. OCFAs production was increased by 12-times; 0.36 versus 0.03 g/L for WT.In summary, Y. lipolytica strains were developed to produce high-amount of OCFAs, mainly heptadecenoic acid. This work paves the way for the microbial production of OCFAs and their derivatives at the industrial scale.
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Submitted on : Wednesday, April 7, 2021 - 12:19:01 PM
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  • HAL Id : tel-03191617, version 1


Young Kyoung Park. Metabolic engineering of the yeast Yarrowia lipolytica for the production of even- and odd-chain fatty acids. Biotechnology. Université Paris-Saclay, 2020. English. ⟨NNT : 2020UPASB010⟩. ⟨tel-03191617⟩



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