Enzymes aid molecular diversity

Nature is the undisputed champion of creating complex organic molecules, many of which humans have used for many years to create medicines. Chemists have spent over a century honing their ability to make molecules that mimic certain properties of natural products and tinkering with natural products to fine-tune their function. A team of chemists led by Rudi Fasan of the University of Texas at Dallas have now taken riffing on natural products to a whole new level ( Chem 2024, DOI: 10.1016/j.chempr.2024.08.003 ). The researchers took parthenolide, a component of the medicinal herb feverfew, and remixed the molecule’s carbon skeleton using engineered enzymes and additional chemical modifications to create 51 completely new compounds with high structural diversity and intriguing anticancer properties. “Instead of making analogs of the parent molecule, we can create entirely new scaffolds,” Fasan says, adding that this is one of his favorite projects to have come out