Light gives enzyme a radical new role

Abstract

Bathing an enzyme in blue-green light has enabled researchers to completely change its catalytic function so that it carries out a ring-forming reaction not found in nature. The team, led by Todd K. Hyster at Princeton University, used this strategy to build a range of cyclic lactams, a motif found in pharmaceuticals and agrochemicals (Science 2019, DOI: 10.1126/science.aaw1143). The chemists worked with a family of enzymes called ene-reductases, which are thought to help certain microbes combat oxidative stress. The enzymes’ large active sites harbor a flavin cofactor that plays an essential role in their natural reaction, transferring a hydride anion and a proton to double bonds to reduce troublesome metabolites. But Hyster’s team found that shining cyan light onto the flavin puts it into an excited state that makes it a potent single-electron reductant. This enables a radical reaction that can transform a variety of α-chloroamides into lactam rings containing