TY - JOUR
T1 - Biosynthesis of selenium-containing small molecules in diverse microorganisms
AU - Kayrouz, Chase M.
AU - Huang, Jonathan
AU - Hauser, Nicole
AU - Seyedsayamdost, Mohammad R.
N1 - Funding Information:
We thank Andy K. L. Nguy for helpful discussions and the Edward C. Taylor 3rd Year Fellowship in Chemistry (to C.M.K.), the Life Sciences Research Foundation Postdoctoral Fellowship sponsored by the Open Philanthropy Project (to J.H.), the Swiss National Science Foundation Early “Postdoc Mobility” Fellowship (no. P2EZP2_187995 to N.H.), the National Science Foundation CAREER Award (no. 1847932 to M.R.S.), and the US National Institutes of Health (GM129496 to M.R.S.) for financial support.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/10/6
Y1 - 2022/10/6
N2 - 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. Here we use a genome-mining strategy in various microorganisms to uncover a widespread three-gene cluster that encodes a dedicated pathway for producing selenoneine, the selenium analogue 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 biosynthetic pathway for production of a selenosugar, which is an unexpected intermediate en 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.
AB - 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. Here we use a genome-mining strategy in various microorganisms to uncover a widespread three-gene cluster that encodes a dedicated pathway for producing selenoneine, the selenium analogue 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 biosynthetic pathway for production of a selenosugar, which is an unexpected intermediate en 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.
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U2 - 10.1038/s41586-022-05174-2
DO - 10.1038/s41586-022-05174-2
M3 - Article
C2 - 36071162
AN - SCOPUS:85137479442
SN - 0028-0836
VL - 610
SP - 199
EP - 204
JO - Nature
JF - Nature
IS - 7930
ER -