6SGL

Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases.

(2020) Nat Chem Biol 16: 556-563

• PubMed: 32066967 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1038/s41589-020-0476-2
• Primary Citation of Related Structures:  
  6SGG, 6SGL, 6SGM, 6SGN, 6TEE, 6TEF, 6TEG


• PubMed Abstract: 
  

  One of the hallmark reactions catalyzed by flavin-dependent enzymes is the incorporation of an oxygen atom derived from dioxygen into organic substrates. For many decades, these flavin monooxygenases were assumed to use exclusively the flavin-C4a-(hydro)peroxide as their oxygen-transferring intermediate. We demonstrate that flavoenzymes may instead employ a flavin-N5-peroxide as a soft α-nucleophile for catalysis, which enables chemistry not accessible to canonical monooxygenases. This includes, for example, the redox-neutral cleavage of carbon-hetero bonds or the dehalogenation of inert environmental pollutants via atypical oxygenations. We furthermore identify a shared structural motif for dioxygen activation and N5-functionalization, suggesting a conserved pathway that may be operative in numerous characterized and uncharacterized flavoenzymes from diverse organisms. Our findings show that overlooked flavin-N5-oxygen adducts are more widespread and may facilitate versatile chemistry, thus upending the notion that flavin monooxygenases exclusively function as nature's equivalents to organic peroxides in synthetic chemistry.

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Organizational Affiliation: 

Faculty of Biology, University of Freiburg, Freiburg, Germany.