A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors
Abstract Dysregulation of lipid metabolism is associated with obesity and metabolic diseases but there is also increasing evidence of a relationship between lipid body excess and cancer. Lipid body synthesis requires diacylglycerol acyltransferases (DGATs) which catalyze the last step of triacylglyc...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | MicrobiologyOpen |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mbo3.1334 |
| _version_ | 1811177951636488192 |
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| author | Peter Gajdoš Rodrigo Ledesma‐Amaro Jean‐Marc Nicaud Tristan Rossignol |
| author_facet | Peter Gajdoš Rodrigo Ledesma‐Amaro Jean‐Marc Nicaud Tristan Rossignol |
| author_sort | Peter Gajdoš |
| collection | DOAJ |
| description | Abstract Dysregulation of lipid metabolism is associated with obesity and metabolic diseases but there is also increasing evidence of a relationship between lipid body excess and cancer. Lipid body synthesis requires diacylglycerol acyltransferases (DGATs) which catalyze the last step of triacylglycerol synthesis from diacylglycerol and acyl‐coenzyme A. The DGATs and in particular DGAT2, are therefore considered 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 DGAT activities, to evaluate the functionality of the enzymes in this heterologous host and DGAT activity inhibitors. This work provides evidence that mammalian DGATs expressed in Y. lipolytica are a useful tool for screening chemical libraries to identify potential inhibitors or activators of these enzymes of therapeutic interest. |
| first_indexed | 2024-04-11T06:09:58Z |
| format | Article |
| id | doaj.art-a35e4c308e6a4c2c8ef6f91f3d8d9401 |
| institution | Directory Open Access Journal |
| issn | 2045-8827 |
| language | English |
| last_indexed | 2024-04-11T06:09:58Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | MicrobiologyOpen |
| spelling | doaj.art-a35e4c308e6a4c2c8ef6f91f3d8d94012022-12-22T04:41:19ZengWileyMicrobiologyOpen2045-88272022-12-01116n/an/a10.1002/mbo3.1334A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitorsPeter Gajdoš0Rodrigo Ledesma‐Amaro1Jean‐Marc Nicaud2Tristan Rossignol3Institute of Biotechnology, Faculty of Chemical and Food Technology Slovak University of Technology Radlinskeho Bratislava SlovakiaDepartment of Bioengineering, Imperial College Centre for Synthetic Biology Imperial College London, South Kensington Campus London UKUniversité Paris‐Saclay, INRAE, AgroParisTech, Micalis Institute Jouy‐en‐Josas FranceUniversité Paris‐Saclay, INRAE, AgroParisTech, Micalis Institute Jouy‐en‐Josas FranceAbstract Dysregulation of lipid metabolism is associated with obesity and metabolic diseases but there is also increasing evidence of a relationship between lipid body excess and cancer. Lipid body synthesis requires diacylglycerol acyltransferases (DGATs) which catalyze the last step of triacylglycerol synthesis from diacylglycerol and acyl‐coenzyme A. The DGATs and in particular DGAT2, are therefore considered 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 DGAT activities, to evaluate the functionality of the enzymes in this heterologous host and DGAT activity inhibitors. This work provides evidence that mammalian DGATs expressed in Y. lipolytica are a useful tool for screening chemical libraries to identify potential inhibitors or activators of these enzymes of therapeutic interest.https://doi.org/10.1002/mbo3.1334acyl‐CoA:diacylglycerol acyltransferaseDGATheterologous expressioninhibitor screeningYarrowia lipolytica |
| spellingShingle | Peter Gajdoš Rodrigo Ledesma‐Amaro Jean‐Marc Nicaud Tristan Rossignol A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors MicrobiologyOpen acyl‐CoA:diacylglycerol acyltransferase DGAT heterologous expression inhibitor screening Yarrowia lipolytica |
| title | A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| title_full | A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| title_fullStr | A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| title_full_unstemmed | A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| title_short | A yeast‐based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| title_sort | yeast based tool for screening mammalian diacylglycerol acyltransferase inhibitors |
| topic | acyl‐CoA:diacylglycerol acyltransferase DGAT heterologous expression inhibitor screening Yarrowia lipolytica |
| url | https://doi.org/10.1002/mbo3.1334 |
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