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Ovoselenol, a Selenium-containing AnOoxidant Derived from Convergent Evolution

Kayrouz, C. M.; Ireland, K. A.; Ying, V.; Davis, K. M.; Seyedsaamdost, M. R.

2024-04-10 biochemistry
10.1101/2024.04.10.588772 bioRxiv
Show abstract

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.

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