Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 698, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2020.108732
Keywords
Flavin monooxygenases; Flavin-dependent monooxygenases; EncM; RutA; Flavin-C4a-peroxide; Flavin-N5-oxide
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [TE 931/3-1, TE 931/4-1, 235777276/GRK1976]
- Fonds zur Forderung der wissenschaftlichen Forschung (FWF) via an Erwin-Schrodinger stipend [J-4482B]
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This paper discusses the structural and mechanistic characteristics of different types of flavoprotein monooxygenases (FPMOs) and their diverse reaction types, as well as the chemical basis of these reactions. Through fine-tuning and functionalization of the flavin cofactor, FPMOs exhibit unparalleled versatility in oxygenation reactions.
The ubiquitous flavoenzymes commonly catalyze redox chemistry such as the monooxygenation of organic substrates and are both widely utilized in nature (e.g., in primary and secondary metabolism) and of significant industrial interest. In this work, we highlight the structural and mechanistic characteristics of the distinct types of flavoprotein monooxygenases (FPMOs). We thereby illustrate the chemical basis of FPMO catalysis, which enables reactions such as (aromatic) hydroxylation, epoxidation, (de)halogenation, heteroatom oxygenation, Baeyer-Villiger oxidation, alpha-hydroxylation of ketones, or non-oxidative carbon-hetero bond cleavage. This seemingly unmatched versatility in oxygenation chemistry results from extensive fine-tuning and regiospecific functionalization of the flavin cofactor that is tightly controlled by the surrounding protein matrix. Accordingly, FPMOs steer the formation of covalent flavin-oxygen adducts for oxygen transfer in the form of the classical flavin-C4a-(hydro)peroxide or the recently discovered N5-functionalized flavins (i.e. the flavin-N5-oxide and the flavin-N5-peroxide), while in rare cases covalent oxygen adduct formation may be foregone entirely. Finally, we speculate about hitherto undiscovered flavin-mediated oxygenation reactions and compare FPMOs to cytochrome P450 monooxygenases, before addressing open questions and challenges for the future investigation of FPMOs.
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