Researchers at the Max Planck Institute for Chemical Ecology in Jena have made significant strides in understanding the biosynthetic pathway responsible for the formation of cardenolides in plants, a critical step in developing sustainable platforms for the production of high-quality steroid compounds for medical applications. Their findings, published in the journal Nature Plants, pinpoint two enzymes from the CYP87A family as crucial catalysts in the creation of pregnenolone, a precursor for plant steroids. This discovery holds promise for the cost-effective and eco-friendly production of medically valuable steroids.
Plants are a rich source of various metabolites, including medically important steroids. Cardenolides, a class of substances with established therapeutic significance, have been derived from plants for centuries. However, despite their diverse applications, the biosynthetic pathways responsible for producing these complex molecules remained largely unknown.
The study focused on two plant species, the foxglove Digitalis purpurea and the rubber tree Calotropis procera, both prolific producers of cardenolides. Unlike model plants with well-documented genomes, these species posed a unique challenge due to limited genetic information.
The research team’s approach was informed by previous work on a related foxglove species, suggesting that cardenolide biosynthesis centers around pregnenolone, a key precursor with links to major steroid hormones in humans.
Comparative analysis of the two plant species’ genomes enabled the identification of candidate genes involved in cardenolide biosynthesis. The team also examined tissue-specific localization of cardenolides, crucial for selecting candidate genes. Ultimately, two enzymes from the cytochrome P450 family 87A were identified as the key catalysts for converting cholesterol and phytosterols into pregnenolone in both plant species.
To validate their findings, researchers genetically modified Arabidopsis thaliana plants to produce more CYP87A enzymes, leading to elevated pregnenolone levels. Conversely, foxglove plants engineered to lack CYP87A enzymes in their leaves displayed reduced pregnenolone and cardenolide production.
The researchers view this discovery as a pivotal step toward unraveling the complex biosynthetic pathway of cardenolides in various plant species. They are already engaged in further research to decode downstream steps in the pathway. By leveraging cutting-edge sequencing, bioinformatics, and metabolomics techniques, the team aims to decipher this intricate puzzle.
The implications of this research extend beyond understanding natural cardenolide production. Enzymes like CYP87A offer potential for the sustainable production of valuable plant compounds, paving the way for more eco-friendly pharmaceutical and chemical processes.
Sarah O’Connor, who leads the Department of Natural Product Biosynthesis at the Max Planck Institute for Chemical Ecology, emphasizes the significance of these findings for sustainable plant compound production. The discovery of enzymes such as CYP87A opens doors to biologically driven platforms that can harness other plant species for the eco-conscious synthesis of high-value compounds.