Discovery of the selenium-containing antioxidant ovoselenol derived from convergent evolution

TY - JOUR

T1 - Discovery of the selenium-containing antioxidant ovoselenol derived from convergent evolution

AU - Kayrouz, Chase M.

AU - Ireland, Kendra A.

AU - Ying, Vanessa Y.

AU - Davis, Katherine M.

AU - Seyedsayamdost, Mohammad R.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.

PY - 2024/11

Y1 - 2024/11

N2 - Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of a biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be discovered. Here we identify a recently evolved branch of abundant and uncharacterized metalloenzymes that we predict are involved in selenometabolite biosynthesis using a bioinformatic search strategy that relies on the mapping of composite active site motifs. Biochemical studies confirm this prediction and show that these enzymes form an unusual C–Se bond onto histidine, thus giving rise to a distinct 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. (Figure presented.)

AB - Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of a biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be discovered. Here we identify a recently evolved branch of abundant and uncharacterized metalloenzymes that we predict are involved in selenometabolite biosynthesis using a bioinformatic search strategy that relies on the mapping of composite active site motifs. Biochemical studies confirm this prediction and show that these enzymes form an unusual C–Se bond onto histidine, thus giving rise to a distinct 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. (Figure presented.)

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U2 - 10.1038/s41557-024-01600-2

DO - 10.1038/s41557-024-01600-2

M3 - Article

C2 - 39143299

SN - 1755-4330

VL - 16

SP - 1868

EP - 1875

JO - Nature chemistry

JF - Nature chemistry

IS - 11

ER -