Tryptophan Lyase (NosL): A Cornucopia of 5′-Deoxyadenosyl Radical Mediated Transformations

Tryptophan lyase (NosL) is a radical S -adenosyl- l -methionine (SAM) enzyme that catalyzes the formation of 3-methyl-2-indolic acid from l -tryptophan. In this paper, we demonstrate that the 5′-deoxyadenosyl radical is considerably more versatile in its chemistry than previously anticipated: hydrogen atom abstraction from N α -cyclopropyltryptophan occurs at Cα rather than the amino group with NosL Y90A and replacing the substrate amine with a ketone or an alkene changes the chemistry from hydrogen atom abstraction to double bond addition. In addition, the 5′-deoxyadenosyl radical can add to the [4Fe−4S] cluster and dithionite can be used to trap radicals at the active site.