Skip to main content
Canna~Fangled Abstracts

Dual cytoplasmic-peroxisomal compartmentalization engineering and multiple metabolic engineering strategies for high yield non-psychoactive cannabinoid in Saccharomyces cerevisiae

By January 1, 2024February 27th, 2024No Comments


doi: 10.1002/biot.202300590.

Affiliations 

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

PubMed Disclaimer

Similar articles

References

REFERENCES

    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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

LinkOut – more resources


Leave a Reply