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Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion
Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex an...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819412/ https://www.ncbi.nlm.nih.gov/pubmed/29358378 http://dx.doi.org/10.1073/pnas.1715282115 |
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author | Ferreira, Raphael Teixeira, Paulo Gonçalves Siewers, Verena Nielsen, Jens |
author_facet | Ferreira, Raphael Teixeira, Paulo Gonçalves Siewers, Verena Nielsen, Jens |
author_sort | Ferreira, Raphael |
collection | PubMed |
description | Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8-fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories. |
format | Online Article Text |
id | pubmed-5819412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-58194122018-02-21 Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion Ferreira, Raphael Teixeira, Paulo Gonçalves Siewers, Verena Nielsen, Jens Proc Natl Acad Sci U S A Biological Sciences Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8-fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories. National Academy of Sciences 2018-02-06 2018-01-22 /pmc/articles/PMC5819412/ /pubmed/29358378 http://dx.doi.org/10.1073/pnas.1715282115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Ferreira, Raphael Teixeira, Paulo Gonçalves Siewers, Verena Nielsen, Jens Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title | Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title_full | Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title_fullStr | Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title_full_unstemmed | Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title_short | Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
title_sort | redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819412/ https://www.ncbi.nlm.nih.gov/pubmed/29358378 http://dx.doi.org/10.1073/pnas.1715282115 |
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