Enzyme coordinates pericyclic trifecta

Abstract

Pericyclic reactions, in which electrons move in concert to rearrange a molecule’s structure, are standard tools for synthetic chemists. But examples of such transformations in nature are fairly rare. Chemists have now identified an enzyme that catalyzes three pericyclic reactions in the biochemical pathway that produces the fungal natural product leporin C. “This really opens up the idea that nature is able to affect reactions of much broader generality than we ever knew before,” says Kendall N. Houk, a University of California, Los Angeles, chemistry professor who led the study along with UCLA’s Yi Tang and University of Shizuoka’s Kenji Watanabe. The enzyme, called LepI, begins by dehydrating a leporin precursor to generate a reactive intermediate. This intermediate, with the help of LepI, can either undergo a hetero-Diels-Alder reaction to produce the desired compound leporin C, or it can perform an intramolecular Diels-Alder reaction to produce a different intermediate that