Biosynthesis of selenium-containing small molecules in diverse microorganisms

Area of Science:

• Biochemistry
• Microbiology
• Natural Products Chemistry

Background:

• Selenium is a vital micronutrient for life.
• Known biological selenium incorporation involves selenocysteine and 2-selenouridine.
• Pathways for selenium incorporation into small molecules were previously unknown.

Purpose of the Study:

• To identify and characterize novel pathways for selenium incorporation into small molecules.
• To uncover the biosynthesis of selenoneine, the selenium analog of ergothioneine.

Main Methods:

• Genome-mining strategy across diverse microorganisms.
• Biochemical characterization of three novel enzymes involved in the pathway.
• Elucidation of a novel biosynthetic route involving a selenosugar intermediate.

Main Results:

• Discovery of a widespread three-gene cluster encoding a dedicated selenoneine biosynthesis pathway.
• Identification of two novel selenium-carbon bond-forming enzymes.
• Characterization of a novel selenosugar as a biosynthetic intermediate.

Conclusions:

• The study reveals a previously unknown pathway for biological selenium utilization.
• The findings suggest a more diverse selenometabolome than previously understood.
• This work lays the foundation for discovering other selenium-containing natural products.