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Ingénierie métabolique de la levure Yarrowia lipolytica pour la production d'acides dicarboxyliques à partir d'huiles végétales

Abstract : Long-chain dicarboxylic acids (DCA) are intermediates of industrial interests (polymers, plastics, lubricants, antibiotics and fragrances) which are difficult to produce by chemical synthesis. The aim of this study is to develop a biotechnological process to produce these compounds by bioconversion of renewable raw material by the yeast Yarrowia lipolytica. In wild type yeast, fatty acids are degraded mainly through the Β-oxidation pathway.
We blocked the Β-oxidation pathway by disruption of the six genes which code the acyl-CoA oxydases thus allowing to reorientate the fatty acids flux towards the ω-oxidation which led to the production of DCA. Further, the improvement of DCA production was obtained by increasing the hydroxylation activity, involved in the first stage of ω-oxidation, by overexpression of genes coding the NADPH cytochrome P450 reductase and the 12 P450 cytochromes. Nevertheless, half of the bioconversion substrate was accumulated in the cytoplasmic lipid bodies. This storage was decreased, by the disruption of two genes, DGA1 and LRO1, involved in this pathway, thus allowing an increase in the bioconversion yield.
Finally, the study of insertion mutants revealed an involvement of 5 ABC transporter of the PDR type family which confer pleiotropic drug resistance. The functional study of this family suggested that the ABC transporter coded by ABC1 gene was a membrane exporter specific for long chain alkanes and represents the first ABC transporter of the PDR type identified responsible for the export of physiological molecules.
Overall, this work has provided the development of a genetically modified strain of Y. lipolytica to produce DCA from vegetable oils.
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Submitted on : Thursday, January 25, 2007 - 3:54:21 PM
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  • HAL Id : tel-00126675, version 1
  • PRODINRA : 246622

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France Thévenieau. Ingénierie métabolique de la levure Yarrowia lipolytica pour la production d'acides dicarboxyliques à partir d'huiles végétales. Biochimie [q-bio.BM]. Institut national agronomique paris-grignon - INA P-G, 2006. Français. ⟨NNT : 2006INAP0022⟩. ⟨tel-00126675⟩

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