Natural deep eutectic solvents enhance cannabinoid biotransformation

Numerous studies in cannabinoid biotechnology focus extensively on cytosolic biosynthesis or biotransforma-tion, neglecting to consider non-aqueous solvents. In this study, we show that it is advantageous to perform cannabinoid biotransformations in natural deep eutectic solvents (NADES). NADES are composed of two or more natural compounds, which, when mixed lower the melting point of the solution significantly below those of the individual components. Thus, initially solid sugars, amino acids, or organic acids are complexed into solvents that are liquids at room temperature. We comprehensively assess these novel green solvents for their capa-bilities to facilitate in vitro biotransformations by the three known cannabinoid synthases. Compared to aqueous biosynthesis, NADES doubled cannabinoid production of tetrahydrocannabinolic acid synthase and more than tripled production of cannabichromenic acid synthase. Data allows us to suggest solvent compositions that flexibly boost total cannabinoid content or alter cannabinoid specificity. This knowledge can equip researchers and bioengineers with the tools to tailor cannabinoid production to their needs without taking on the demanding task of enzyme engineering.

Automated summary

This study demonstrates the advantages of performing cannabinoid biotransformations in natural deep eutectic solvents (NADES), which significantly increase cannabinoid production. The research also suggests flexible manipulation of solvent compositions to enhance total cannabinoid content or alter cannabinoid specificity.