Catalytic Promiscuity of the Radical S-adenosyl-L-methionine Enzyme NosL

Abstract

Catalytic promiscuity plays a key role in enzyme evolution and the acquisition of novel biological functions. Because of the high reactivity of radical species, in our view enzymes involving radical-mediated mechanisms could intrinsically be more prone to catalytic promiscuity. This mini-review summarizes the recent advances in the study of NosL, a radical S-adenosyl-L-methionine (SAM)-dependent L-tryptophan (L-Trp) lyase. We demonstrate here the interesting chemistry and remarkable catalytic promiscuity of NosL, and attempt to highlight the high evolvability of radical SAM enzymes and the potential to engineer these enzymes for novel and improved activities.

Keywords: biosynthesis; enzyme engineering; evolution; metalloenzyme; promiscuity.

Figure 1

NosL-catalyzed MIA biosynthesis. (A) Proposed mechanism for NosL catalysis. The two fragmentation patterns of L-Trp are shown in green and blue, respectively. The key radical intermediate identified by Nicolet et al. (Sicoli et al., 2016) is shown in a yellow box. (B) The active site architecture of NosL (PDB ID: 4R33).

Figure 2

Catalytic promiscuity of NosL. (A–H) shows the in vitro reactions of various L-Trp analogs with NosL wild type or mutant enzymes. Simultaneous cleavage of both the Cα-Cβ and Cα-COO(H) bonds have been observed in most cases.