Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica
Abstract Background β-Caryophyllene, a sesquiterpenoid, holds considerable potential in pharmaceutical, nutraceutical, cosmetic, and chemical industries. In order to overcome the limitation of β-caryophyllene production by the extraction from plants or chemical synthesis, we aimed the microbial prod...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-025-02660-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861496818434048 |
|---|---|
| author | Young-Kyoung Park Lucie Studena Piotr Hapeta Ramdane Haddouche David J. Bell Pablo Torres-Montero Jose Luis Martinez Jean-Marc Nicaud Adriana Botes Rodrigo Ledesma-Amaro |
| author_facet | Young-Kyoung Park Lucie Studena Piotr Hapeta Ramdane Haddouche David J. Bell Pablo Torres-Montero Jose Luis Martinez Jean-Marc Nicaud Adriana Botes Rodrigo Ledesma-Amaro |
| author_sort | Young-Kyoung Park |
| collection | DOAJ |
| description | Abstract Background β-Caryophyllene, a sesquiterpenoid, holds considerable potential in pharmaceutical, nutraceutical, cosmetic, and chemical industries. In order to overcome the limitation of β-caryophyllene production by the extraction from plants or chemical synthesis, we aimed the microbial production of β-caryophyllene in non-conventional yeast Yarrowia lipolytica in this study. Results Two genes, tHMG1 from S. cerevisiae to boost the mevalonate pool and QHS1 from Artemisia annua, were expressed under different promoters and copy numbers in Y. lipolytica. The co-expression of 8UAS pEYK1-QHS1 and pTEF-tHMG1 in the obese strain yielded 165.4 mg/L and 201.5 mg/L of β-caryophyllene in single and double copies, respectively. Employing the same combination of promoters and genes in wild-type-based strain with two copies resulted in a 1.36-fold increase in β-caryophyllene. The introduction of an additional three copies of 8UAS pEYK1-tHMG1 further augmented the β-caryophyllene, reaching 318.5 mg/L in flask fermentation. To maximize the production titer, we optimized the carbon source ratio between glucose and erythritol as well as fermentation condition that led to 798.1 mg/L of β-caryophyllene. Conclusions A biosynthetic pathway of β-caryophyllene was firstly investigated in Y. lipolytica in this study. Through the modulation of key enzyme expression, we successfully demonstrated an improvement in β-caryophyllene production. This strategy suggests its potential extension to studies involving the microbial production of various industrially relevant terpenes. |
| format | Article |
| id | doaj-art-ba0b78667f06474faa68084583b5c3d9 |
| institution | Kabale University |
| issn | 1475-2859 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj-art-ba0b78667f06474faa68084583b5c3d92025-02-09T13:00:51ZengBMCMicrobial Cell Factories1475-28592025-02-012411810.1186/s12934-025-02660-wEfficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolyticaYoung-Kyoung Park0Lucie Studena1Piotr Hapeta2Ramdane Haddouche3David J. Bell4Pablo Torres-Montero5Jose Luis Martinez6Jean-Marc Nicaud7Adriana Botes8Rodrigo Ledesma-Amaro9Department of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College LondonDepartment of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College LondonDepartment of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College LondonVideraBio LtdSynbiCITE Innovation and Knowledge Centre, Imperial College LondonDepartment of Biotechnology and Biomedicine, Section for Synthetic Biology, Technical University of DenmarkDepartment of Biotechnology and Biomedicine, Section for Synthetic Biology, Technical University of DenmarkUniversité Paris-Saclay, INRAE, AgroParisTech, Micalis InstituteVideraBio LtdDepartment of Bioengineering and Imperial College Centre for Synthetic Biology, Imperial College LondonAbstract Background β-Caryophyllene, a sesquiterpenoid, holds considerable potential in pharmaceutical, nutraceutical, cosmetic, and chemical industries. In order to overcome the limitation of β-caryophyllene production by the extraction from plants or chemical synthesis, we aimed the microbial production of β-caryophyllene in non-conventional yeast Yarrowia lipolytica in this study. Results Two genes, tHMG1 from S. cerevisiae to boost the mevalonate pool and QHS1 from Artemisia annua, were expressed under different promoters and copy numbers in Y. lipolytica. The co-expression of 8UAS pEYK1-QHS1 and pTEF-tHMG1 in the obese strain yielded 165.4 mg/L and 201.5 mg/L of β-caryophyllene in single and double copies, respectively. Employing the same combination of promoters and genes in wild-type-based strain with two copies resulted in a 1.36-fold increase in β-caryophyllene. The introduction of an additional three copies of 8UAS pEYK1-tHMG1 further augmented the β-caryophyllene, reaching 318.5 mg/L in flask fermentation. To maximize the production titer, we optimized the carbon source ratio between glucose and erythritol as well as fermentation condition that led to 798.1 mg/L of β-caryophyllene. Conclusions A biosynthetic pathway of β-caryophyllene was firstly investigated in Y. lipolytica in this study. Through the modulation of key enzyme expression, we successfully demonstrated an improvement in β-caryophyllene production. This strategy suggests its potential extension to studies involving the microbial production of various industrially relevant terpenes.https://doi.org/10.1186/s12934-025-02660-wΒ-caryophylleneYarrowia LipolyticaTerpeneBioproductionSynthetic biology |
| spellingShingle | Young-Kyoung Park Lucie Studena Piotr Hapeta Ramdane Haddouche David J. Bell Pablo Torres-Montero Jose Luis Martinez Jean-Marc Nicaud Adriana Botes Rodrigo Ledesma-Amaro Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica Microbial Cell Factories Β-caryophyllene Yarrowia Lipolytica Terpene Bioproduction Synthetic biology |
| title | Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica |
| title_full | Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica |
| title_fullStr | Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica |
| title_full_unstemmed | Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica |
| title_short | Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica |
| title_sort | efficient biosynthesis of β caryophyllene by engineered yarrowia lipolytica |
| topic | Β-caryophyllene Yarrowia Lipolytica Terpene Bioproduction Synthetic biology |
| url | https://doi.org/10.1186/s12934-025-02660-w |
| work_keys_str_mv | AT youngkyoungpark efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT luciestudena efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT piotrhapeta efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT ramdanehaddouche efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT davidjbell efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT pablotorresmontero efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT joseluismartinez efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT jeanmarcnicaud efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT adrianabotes efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica AT rodrigoledesmaamaro efficientbiosynthesisofbcaryophyllenebyengineeredyarrowialipolytica |