Synthetic secrets of catnip compound revealed

Abstract

Nepetalactone is a cyclic monoterpene best known for instigating the euphoric frenzy that cats and other felines experience when they smell catnip. Now, researchers have discovered that catnip and other plants in the Nepeta genus cyclize the molecule via an unusual two-step pathway (Nat. Chem. Biol. 2018, DOI: 10.1038/s41589-018-0185-2). The discovery may help synthetic biologists engineer microbes to efficiently synthesize closely related molecules that have anticancer and anti-inflammatory properties. Normally, organisms make cyclic monoterpenes with the help of terpene synthase, an enzyme that activates and cyclizes a precursor, geranyl diphosphate, through a cationic intermediate. But nepetalactone is synthesized a little differently: a precursor, 8-oxogeranial, undergoes a reduction before cyclizing. In 2012, Sarah O’Connor, a biochemist at the John Innes Center, discovered iridoid synthase, the enzyme she credited with doing the job. She and her colleagues now report that the pathway is odder than t...