Systematic biotechnological production of isoprenoid analogs with bespoke carbon skeletons.

Summary

The authors present a yeast-based biocatalytic platform that systematically introduces extra carbons into diverse isoprenoid classes, enabling production of analogs with tailored properties. Proof-of-concept includes biosynthesis of ethyllinalool and cannabinoid analogs with enhanced receptor agonism, highlighting broad utility for fragrance and bioactive discovery.

Key Findings

• Developed a yeast cell-based method to produce isoprenoid analogs (monoterpenoids, sesquiterpenoids, triterpenoids, cannabinoids) with additional carbon atoms.
• Demonstrated biosynthesis of ethyllinalool and cannabinoid analogs exhibiting improved cannabinoid receptor agonism.
• Platform is simple, adaptable to diverse cell factories, and expands isoprenoid chemical space to identify molecules with improved properties.

Clinical Implications

While preclinical, this approach accelerates access to novel fragrance and bioactive candidates with potentially improved safety or efficacy profiles, informing dermatology-adjacent product pipelines (e.g., topical actives) and precision formulation.

Limitations

• Primarily preclinical with limited in vivo validation of analog safety/efficacy.
• Manufacturing economics and regulatory pathways for novel analogs remain to be defined.

Future Directions

Integrate cheminformatics-guided design and high-throughput screening to prioritize analogs with superior dermatologic and safety profiles; evaluate scale-up fermentation and downstream purification for industrial deployment.