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A yeast-based tool for mammalian DGATs inhibitors screening

Peter Gajdoš, View ORCID ProfileRodrigo Ledesma-Amaro, View ORCID ProfileJean-Marc Nicaud, View ORCID ProfileTristan Rossignol
doi: https://doi.org/10.1101/2022.07.06.498986
Peter Gajdoš
1Institute of Biotechnology, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, 812 37 Bratislava, Slovakia
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Rodrigo Ledesma-Amaro
2Imperial College Centre for Synthetic Biology and Department of Bioengineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
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Jean-Marc Nicaud
3Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France., France
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Tristan Rossignol
3Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France., France
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  • ORCID record for Tristan Rossignol
  • For correspondence: tristan.rossignol@inrae.fr
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Abstract

Dysregulation of lipid metabolism is associated with obesity, metabolic diseases but there is also increasing evidences of a relationship between lipid bodies (LBs) excess and some cancer. LBs synthesis requires diacylglycerol acyltransferases (DGATs) which catalyses the last step of triacylglycerol (TAG) synthesis, the main storage lipid form in lipid bodies. DGATs and in particular DGAT2, are therefore considered as potential therapeutic targets for the control of these pathologies. Here, the murine and the human DGAT2 were overexpressed in the oleaginous yeast Yarrowia lipolytica deleted for all DGATs activities, for evaluating the functionality of the enzymes in this heterologous host and to evaluate DGAT activity inhibitors. This work provide evidence that mammalian DGATs expressed in Y. lipolytica is a useful tool for screening chemical libraries to identify potential inhibitors or activators of these enzymes of therapeutic interest.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 06, 2022.
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A yeast-based tool for mammalian DGATs inhibitors screening
Peter Gajdoš, Rodrigo Ledesma-Amaro, Jean-Marc Nicaud, Tristan Rossignol
bioRxiv 2022.07.06.498986; doi: https://doi.org/10.1101/2022.07.06.498986
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A yeast-based tool for mammalian DGATs inhibitors screening
Peter Gajdoš, Rodrigo Ledesma-Amaro, Jean-Marc Nicaud, Tristan Rossignol
bioRxiv 2022.07.06.498986; doi: https://doi.org/10.1101/2022.07.06.498986

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