Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
29
08
2019
accepted:
08
01
2020
pubmed:
19
2
2020
medline:
21
7
2020
entrez:
19
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32066967
doi: 10.1038/s41589-020-0476-2
pii: 10.1038/s41589-020-0476-2
doi:
Substances chimiques
Dinitrocresols
0
Escherichia coli Proteins
0
Peroxides
0
4,6-dinitro-o-cresol
1604ZJR09T
Oxygenases
EC 1.13.-
Ruta protein, E coli
EC 1.13.-
dimethylaniline monooxygenase (N-oxide forming)
EC 1.14.13.8
dibenzothiophene sulfone monooxygenase
EC 1.14.99.-
Nitrogen
N762921K75
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
556-563Subventions
Organisme : NIGMS NIH HHS
ID : F32 GM122218
Pays : United States
Commentaires et corrections
Type : CommentIn
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