- PMID: 38375558
- DOI: 10.1002/biot.202300590
Abstract
CBG (Cannabigerol), a nonpsychoactive cannabinoid, has garnered attention due to its extensive antimicrobial and anti-inflammatory properties. However, the natural content of CBG in Cannabis sativa L. is minimal. In this study, we developed an engineered cell factory for CBG production using Saccharomyces cerevisiae. We introduced the CBGA biosynthetic pathway into S. cerevisiae and employed several strategies to enhance CBGA production. These strategies included dynamically inhibiting the competitive bypass of key metabolic pathways regulated by Erg20p. Additionally, we implemented a dual cytoplasmic-peroxisomal compartmentalization approach to further increase CBGA production. Furthermore, we ensured efficient CBGA production by optimizing NADPH and acetyl-CoA pools. Ultimately, our engineered strain achieved a CBG titer of 138 mg L-1 through fed-batch fermentation in a 5 L bioreactor, facilitated by microwave decarboxylation extraction. These findings underscore the significant potential of yeast cell factories for achieving higher yields in cannabinoid production.
Keywords: NAPDH, Saccharomyces cerevisiae, acetyl-CoA, cannabigerol, dual cytoplasmic-peroxisomal compartmentalization
© 2024 Wiley-VCH GmbH.
Similar articles
-
Harnessing Yeast Peroxisomes and Cytosol Acetyl-CoA for Sesquiterpene α-Humulene Production.J Agric Food Chem. 2020 Feb 5;68(5):1382-1389. doi: 10.1021/acs.jafc.9b07290. Epub 2020 Jan 24.PMID: 31944688
-
Metabolic Engineering and Adaptive Evolution for Efficient Production of l-Lactic Acid in Saccharomyces cerevisiae.Microbiol Spectr. 2022 Dec 21;10(6):e0227722. doi: 10.1128/spectrum.02277-22. Epub 2022 Nov 10.PMID: 36354322 Free PMC article.
-
Biosynthesis and engineering of kaempferol in Saccharomyces cerevisiae.Microb Cell Fact. 2017 Sep 26;16(1):165. doi: 10.1186/s12934-017-0774-x.PMID: 28950867 Free PMC article.
-
Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: Pathway stoichiometry, free-energy conservation and redox-cofactor balancing.Metab Eng. 2016 Jul;36:99-115. doi: 10.1016/j.ymben.2016.03.006. Epub 2016 Mar 23.PMID: 27016336 Review.
-
Bioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeast.Appl Microbiol Biotechnol. 2020 Nov;104(22):9551-9563. doi: 10.1007/s00253-020-10798-3. Epub 2020 Oct 12.PMID: 33043390 Free PMC article. Review.
References
REFERENCES
-
- Crippa, J. A. S., Zuardi, A. W., Guimaraes, F. S., Campos, A. C., Osorio, F. D., Loureiro, S. R., Dos Santos, R. G., Souza, J. D. S., Ushirohira, J. M., Pacheco, J. C., Ferreira, R. R., Costa, K. C. M., Scomparin, D. S., Scarante, F. F., Pires-Dos-Santos, I., Mechoulam, R., Kapczinski, F., Fonseca, B. A. L., Esposito, D. L. A., … Cannab, B. D. P. (2021). Efficacy and safety of cannabidiol plus standard care vs standard care alone for the treatment of emotional exhaustion and burnout among frontline health care workers during the COVID-19 pandemic. Jama Network Open, 4, e2120603-e2120603.
- Zhang, X. Y., Xu, G. C., Cheng, C. H., Lei, L., Sun, J., Xu, Y., Deng, C. H., Dai, Z. G., Yang, Z. M., Chen, X. J., Liu, C., Tang, Q., & Su, J. G. (2021). Establishment of an agrobacterium – mediated genetic transformation and CRISPR/Cas9-mediated targeted mutagenesis in Hemp (Cannabis Sativa L.). Plant Biotechnology Journal, 19, 1979-1987.
- Brierley, D. I., Harman, J. R., Giallourou, N., Leishman, E., Roashan, A. E., Mellows, B. A. D., Bradshaw, H. B., Swann, J. R., Patel, K., Whalley, B. J., & Williams, C. M. (2019). Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol. Journal of Cachexia Sarcopenia and Muscle, 10, 844-859.
- Ahuja, C. S., Nori, S., Tetreault, L., Wilson, J., Kwon, B., Harrop, J., Choi, D., & Fehlings, M. G. (2017). Traumatic spinal cord injury-Repair and regeneration. Neurosurgery, 80, S9-S22.
- Mahmoud, A. M., Kostrzewa, M., Marolda, V., Cerasuolo, M., Maccarinelli, F., Coltrini, D., Rezzola, S., Giacomini, A., Mollica, M. P., Motta, A., Paris, D., Zorzano, A., Di Marzo, V., Ronca, R., & Ligresti, A. (2023). Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer. Pharmacological Research, 189, 106683.
MeSH terms
Substances
Grants and funding
LinkOut – more resources
-
Research Materials
-
Miscellaneous