Flavin-dependent N-hydroxylating enzymes : distribution and application
Amino groups derived from naturally abundant amino acids or (di)amines can be used as “shuttles” in nature for oxygen transfer to provide intermediates or products comprising N-O functional groups such as N-hydroxy, oxazine, isoxazolidine, nitro, nitrone, oxime, C-, S-, or N-nitroso, and azoxy units. To this end, molecular oxygen is activated by flavin, heme, or metal cofactor-containing enzymes and transferred to initially obtain N-hydroxy compounds, which can be further functionalized. In this review, we focus on flavin-dependent N-hydroxylating enzymes, which play a major role in the production of secondary metabolites, such as siderophores or antimicrobial agents. Flavoprotein monooxygenases of higher organisms (among others, in humans) can interact with nitrogen-bearing secondary metabolites or are relevant with respect to detoxification metabolism and are thus of importance to understand potential medical applications. Many enzymes that catalyze N-hydroxylation reactions have specific substrate scopes and others are rather relaxed. The subsequent conversion towards various N-O or N-N comprising molecules is also described. Overall, flavin-dependent N-hydroxylating enzymes can accept amines, diamines, amino acids, amino sugars, and amino aromatic compounds and thus provide access to versatile families of compounds containing the N-O motif. Natural roles as well as synthetic applications are highlighted.• N-O and N-N comprising natural and (semi)synthetic products are highlighted.• Flavin-based NMOs with respect to mechanism, structure, and phylogeny are reviewed.• Applications in natural product formation and synthetic approaches are provided. [Figure not available: see fulltext.].
| Main Authors: | , , , , , |
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| Format: | Article/Letter to editor biblioteca |
| Language: | English |
| Subjects: | Bioactive compounds, Biocatalysis, Biotransformation, Flavoproteins, Monooxygenases, N-Hydroxylases, Phylogenetics, Siderophores, |
| Online Access: | https://research.wur.nl/en/publications/flavin-dependent-n-hydroxylating-enzymes-distribution-and-applica |
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| Summary: | Amino groups derived from naturally abundant amino acids or (di)amines can be used as “shuttles” in nature for oxygen transfer to provide intermediates or products comprising N-O functional groups such as N-hydroxy, oxazine, isoxazolidine, nitro, nitrone, oxime, C-, S-, or N-nitroso, and azoxy units. To this end, molecular oxygen is activated by flavin, heme, or metal cofactor-containing enzymes and transferred to initially obtain N-hydroxy compounds, which can be further functionalized. In this review, we focus on flavin-dependent N-hydroxylating enzymes, which play a major role in the production of secondary metabolites, such as siderophores or antimicrobial agents. Flavoprotein monooxygenases of higher organisms (among others, in humans) can interact with nitrogen-bearing secondary metabolites or are relevant with respect to detoxification metabolism and are thus of importance to understand potential medical applications. Many enzymes that catalyze N-hydroxylation reactions have specific substrate scopes and others are rather relaxed. The subsequent conversion towards various N-O or N-N comprising molecules is also described. Overall, flavin-dependent N-hydroxylating enzymes can accept amines, diamines, amino acids, amino sugars, and amino aromatic compounds and thus provide access to versatile families of compounds containing the N-O motif. Natural roles as well as synthetic applications are highlighted.• N-O and N-N comprising natural and (semi)synthetic products are highlighted.• Flavin-based NMOs with respect to mechanism, structure, and phylogeny are reviewed.• Applications in natural product formation and synthetic approaches are provided. [Figure not available: see fulltext.]. |
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