Biology subjects

Kayrouz, C. M.

Publications and source records attributed to Kayrouz, C. M..

2 recordsLinked to original sources

bioRxiv2024

Ovoselenol, a Selenium-containing AnOoxidant Derived from Convergent Evolution

Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of the first biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be discovered. Using a bioinformatic search strategy that relies on mapping of composite active site motifs, we identify a recently evolved branch of abundant and uncharacterized metalloenzymes that we predict are involved in selenometabolite biosynthesis. Biochemical studies confirm this prediction and show that these enzymes form an unusual C-Se bond onto histidine, thus giving rise to a novel selenometabolite and potent antioxidant that we have termed ovoselenol. Aside from providing insights into the evolution of this enzyme class and the structural basis of C-Se bond formation, our work offers a blueprint for charting the microbial selenometabolome in the future.

biochemistry↗

bioRxiv2022

A Novel and Prevalent Pathway in Microbial Selenium Metabolism

Selenium is an essential micronutrient in diverse organisms. Two routes are known for its insertion into proteins and nucleic acids via selenocysteine and 2-selenouridine, respectively1. However, despite its importance, pathways for specific incorporation of selenium into small molecules have remained elusive. We herein use a genome mining strategy to uncover a widespread three-gene cluster in varied microorganisms that encodes a dedicated pathway for producing selenoneine, the selenium-analog of the multifunctional molecule ergothioneine2,3. We elucidate the reactions of all three proteins and uncover two novel selenium-carbon bond-forming enzymes and the first biosynthetic pathway for production of a selenosugar, an unexpected intermediate on route to the final product. Our findings expand the scope of biological selenium utilization, suggest that the selenometabolome is more diverse than previously thought, and set the stage for the discovery of other selenium-containing natural products.

biochemistry↗