Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica
Microbial production of lipids is one of the promising alternatives to fossil resources with increasing environmental and energy concern. Odd-chain fatty acids (OCFA), a type of unusual lipids, are recently gaining a lot of interest as target compounds in microbial production due to their diverse ap...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Metabolic Engineering Communications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214030120300584 |
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| author | Young-Kyoung Park Florence Bordes Fabien Letisse Jean-Marc Nicaud |
| author_facet | Young-Kyoung Park Florence Bordes Fabien Letisse Jean-Marc Nicaud |
| author_sort | Young-Kyoung Park |
| collection | DOAJ |
| description | Microbial production of lipids is one of the promising alternatives to fossil resources with increasing environmental and energy concern. Odd-chain fatty acids (OCFA), a type of unusual lipids, are recently gaining a lot of interest as target compounds in microbial production due to their diverse applications in the medical, pharmaceutical, and chemical industries. In this study, we aimed to enhance the pool of precursors with three-carbon chain (propionyl-CoA) and five-carbon chain (β-ketovaleryl-CoA) for the production of OCFAs in Yarrowia lipolytica. We evaluated different propionate-activating enzymes and the overexpression of propionyl-CoA transferase gene from Ralstonia eutropha increased the accumulation of OCFAs by 3.8 times over control strain, indicating propionate activation is the limiting step of OCFAs synthesis. It was shown that acetate supplement was necessary to restore growth and to produce a higher OCFA contents in total lipids, suggesting the balance of the precursors between acetyl-CoA and propionyl-CoA is crucial for OCFA accumulation. To improve β-ketovaleryl-CoA pools for further increase of OCFA production, we co-expressed the bktB encoding β-ketothiolase in the producing strain, and the OCFA production was increased by 33% compared to control. Combining strain engineering and the optimization of the C/N ratio promoted the OCFA production up to 1.87 g/L representing 62% of total lipids, the highest recombinant OCFAs titer reported in yeast, up to date. This study provides a strong basis for the microbial production of OCFAs and its derivatives having high potentials in a wide range of applications. |
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| format | Article |
| id | doaj.art-d29cc41962cd459b94a4e33f57618a3f |
| institution | Directory Open Access Journal |
| issn | 2214-0301 |
| language | English |
| last_indexed | 2024-12-17T00:25:18Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolic Engineering Communications |
| spelling | doaj.art-d29cc41962cd459b94a4e33f57618a3f2022-12-21T22:10:28ZengElsevierMetabolic Engineering Communications2214-03012021-06-0112e00158Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolyticaYoung-Kyoung Park0Florence Bordes1Fabien Letisse2Jean-Marc Nicaud3Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France; Corresponding author. Domaine de vilvert, Batiment 526, Jouy-en-Josas, 78352, France.Toulouse Biotechnology Institute, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, FranceToulouse Biotechnology Institute, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France; Université Toulouse III - Paul Sabatier, Toulouse, FranceUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, FranceMicrobial production of lipids is one of the promising alternatives to fossil resources with increasing environmental and energy concern. Odd-chain fatty acids (OCFA), a type of unusual lipids, are recently gaining a lot of interest as target compounds in microbial production due to their diverse applications in the medical, pharmaceutical, and chemical industries. In this study, we aimed to enhance the pool of precursors with three-carbon chain (propionyl-CoA) and five-carbon chain (β-ketovaleryl-CoA) for the production of OCFAs in Yarrowia lipolytica. We evaluated different propionate-activating enzymes and the overexpression of propionyl-CoA transferase gene from Ralstonia eutropha increased the accumulation of OCFAs by 3.8 times over control strain, indicating propionate activation is the limiting step of OCFAs synthesis. It was shown that acetate supplement was necessary to restore growth and to produce a higher OCFA contents in total lipids, suggesting the balance of the precursors between acetyl-CoA and propionyl-CoA is crucial for OCFA accumulation. To improve β-ketovaleryl-CoA pools for further increase of OCFA production, we co-expressed the bktB encoding β-ketothiolase in the producing strain, and the OCFA production was increased by 33% compared to control. Combining strain engineering and the optimization of the C/N ratio promoted the OCFA production up to 1.87 g/L representing 62% of total lipids, the highest recombinant OCFAs titer reported in yeast, up to date. This study provides a strong basis for the microbial production of OCFAs and its derivatives having high potentials in a wide range of applications.http://www.sciencedirect.com/science/article/pii/S2214030120300584Odd-chain fatty acids (OCFAs)Propionyl-CoAAcetyl-CoAPrecursor poolYarrowia lipolyticaMetabolic engineering |
| spellingShingle | Young-Kyoung Park Florence Bordes Fabien Letisse Jean-Marc Nicaud Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica Metabolic Engineering Communications Odd-chain fatty acids (OCFAs) Propionyl-CoA Acetyl-CoA Precursor pool Yarrowia lipolytica Metabolic engineering |
| title | Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica |
| title_full | Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica |
| title_fullStr | Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica |
| title_full_unstemmed | Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica |
| title_short | Engineering precursor pools for increasing production of odd-chain fatty acids in Yarrowia lipolytica |
| title_sort | engineering precursor pools for increasing production of odd chain fatty acids in yarrowia lipolytica |
| topic | Odd-chain fatty acids (OCFAs) Propionyl-CoA Acetyl-CoA Precursor pool Yarrowia lipolytica Metabolic engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2214030120300584 |
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