Efficient biosynthesis of β-caryophyllene by engineered Yarrowia lipolytica
2025
Park, Young-Kyoung | Studena, Lucie | Hapeta, Piotr | Haddouche, Ramdane | Bell, David, J | Torres-Montero, Pablo | Martinez, Jose Luis | Nicaud, Jean-Marc | Botes, Adriana | Ledesma-Amaro, Rodrigo | Department of Bioengineering [Imperial College London] ; Imperial College London | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | VideraBio Ltd | Imperial College London | Danmarks Tekniske Universitet = Technical University of Denmark (DTU) | BBSRC : BB/R01602X/1, BB/T013176/1, BB/T011408/1 - 19-ERACoBioTech- 33 SyCoLim, BB/X01911X/1, BB/Y008510/1 –Engineering Biology Hub for Microbial Foods), EPSRC (AI-4-EB BB/W013770/1and EEBio Programme Grant EP/Y014073/1 | Yeast4Bio Cost Action 18229 | European Research Council (ERC) (DEUSBIO - 949080) | Bio-based Industries Joint (PERFECOAT- 101022370) under the European Union’s Horizon 2020research and innovation programme and the European Innovation Council (EIC) under grant agreement No. 101098826 (SKINDEV) | Imperial College London UKRI Impact Acceleration Account EPSRC –EP/X52556X/1 | Bezos Earth Fund for their support to the Bezos Centre for Sustainable Protein
International audience
Afficher plus [+] Moins [-]anglais. 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. ResultsTwo 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. ConclusionsA 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.
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