Cannabis research has increased across the globe in recent years, and that research has helped humans better understand the cannabis plant and its potential benefits to society. One area of focus for cannabis research that is still largely in the early stages revolves around cannabinoid oxidocyclases.

A team of researchers affiliated with Wageningen University and Research (WUR) in the Netherlands recently conducted an investigation focusing on cannabinoid oxidocyclases. Their findings were published in the academic publication Plant Biotechnology Journal.

“Cannabinoids, such as tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA), are bioactive and medicinally relevant compounds found in the cannabis plant (Cannabis sativa L.). These three compounds are synthesised from a single precursor, cannabigerolic acid (CBGA), through regioselective reactions catalysed by different cannabinoid oxidocyclase enzymes.” the researchers wrote in their abstract.

“Despite the importance of cannabinoid oxidocyclases for determining cannabis chemotype and properties, the functional evolution and molecular mechanism of this enzyme family remain poorly understood. To address this gap, we combined ancestral sequence reconstruction and heterologous expression to resurrect and functionally characterise three ancestral cannabinoid oxidocyclases.” they wrote about their methodology.

“Results showed that the ability to metabolise CBGA originated in a recent ancestor of cannabis and that early cannabinoid oxidocyclases were promiscuous enzymes producing all three THCA, CBDA and CBCA. Gene duplication and diversification later facilitated enzyme subfunctionalisation, leading to extant, highly-specialised THCA and CBDA synthases.” the researchers found.

“What was once evolutionarily ‘unfinished’ has now proven to be very useful. These ancestral enzymes are more robust and flexible than their descendants, making them very attractive as a starting point for new applications in biotechnology and pharmaceuticals,” stated WUR researcher Robin van Velzen, according to the university’s website.

“Overall, this study contributes to understanding the origin, evolution and molecular mechanism of cannabinoid oxidocyclases, which opens new perspectives for breeding, biotechnological and medicinal applications.” they concluded.