{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:17:41Z","timestamp":1788434261598,"version":"build-2803163510"},"reference-count":102,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The ubiquitous flavoenzymes typically function as oxidoreductases that comprise several distinct main types, including flavoprotein oxidases (FPOs), flavoprotein dehydrogenases (FPDs), and flavoprotein monooxygenases (FPMOs). FPOs and FPDs catalyze two-electron oxidation reactions of organic substrates, typically dehydrogenations, thereby converting oxidized flavin (Flox) into its fully reduced state (Flred). Prior to the next catalytic cycle, molecular oxygen (=dioxygen or O2) or (protein-bound) cofactors facilitate the required Flred reoxidation for FPOs and FPDs. Remarkably, members of these two flavoenzyme types can be homologous with highly similar amino acid compositions and overall structures, as minor protein alterations, particularly in the vicinity of the flavin cofactor, can drastically affect O2 reactivity. Finally, FPMOs incorporate one O2-derived oxygen atom into their substrate. To this end, required electrons for Flred formation and O2 activation either come from NAD(P)H (external FPMOs) or, more rarely, the substrate itself (internal FPMOs). External FPMOs steer O2 reactivity toward the formation of covalent flavin-oxygen adducts primarily at the C4a atom of the flavin\u2019s isoalloxazine ring or, in some cases, at the adjacent N5. In contrast, typical internal FPMOs forego the formation of covalent oxygen adducts entirely, although an exception in the form of a flavin-N5-oxide-forming enzyme has been reported. Consequently, natural selection has led to three distinct O2 reactivity patterns in flavoenzymes, which either suppress (FPDs), stimulate (FPOs), or steer (FPMOs) this challenging process. In this review, current knowledge on the relationship between flavoenzymes and O2 is summarized, emphasizing strategies to insert oxygen into organic substrates and counteract uncoupling, while also highlighting open questions and future challenges.<\/jats:p>","DOI":"10.1021\/acs.biochem.6c00522","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T21:02:10Z","timestamp":1786395730000},"page":"2644-2655","source":"Crossref","is-referenced-by-count":0,"title":["Suppress, Stimulate,\nor Steer: Dioxygen Activation\nby Flavoenzymes and Their Oxygenation Strategies"],"prefix":"10.1021","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-7248","authenticated-orcid":true,"given":"Robin","family":"Teufel","sequence":"first","affiliation":[{"name":"University of Basel , , Klingelbergstrasse 50 , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026090306411055600_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2024.105831","article-title":"Monoamine\noxidase and neurodegeneration: Mechanisms, inhibitors and natural\ncompounds for therapeutic intervention","volume":"179","author":"Banerjee","year":"2024","journal-title":"Neurochem.\nInt."},{"issue":"10","key":"2026090306411055600_cit2","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/nchembio.1633","article-title":"Photochemistry\nof flavoprotein light\nsensors","volume":"10","author":"Conrad","year":"2014","journal-title":"Nat. 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Chem.\nSoc."},{"issue":"33","key":"2026090306411055600_cit36","doi-asserted-by":"publisher","first-page":"8485","DOI":"10.1021\/bi801039d","article-title":"Detection of a C4a-hydroperoxyflavin\nintermediate in the reaction of a flavoprotein oxidase","volume":"47","author":"Sucharitakul","year":"2008","journal-title":"Biochemistry"},{"issue":"1","key":"2026090306411055600_cit37","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1046\/j.1432-1327.1998.2520090.x","article-title":"Glucose\noxidase from Penicillium\namagasakiense. Primary structure and comparison with other glucose-methanol-choline\n(GMC) oxidoreductases","volume":"252","author":"Kiess","year":"1998","journal-title":"Eur. J. Biochem."},{"issue":"1","key":"2026090306411055600_cit38","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1073\/pnas.252644599","article-title":"Catalysis of electron transfer during activation of\nO2 by the flavoprotein glucose oxidase","volume":"100","author":"Roth","year":"2003","journal-title":"Proc.\nNatl. Acad. Sci. U. S. A."},{"issue":"4","key":"2026090306411055600_cit39","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/(SICI)1097-0134(199704)27:4&lt;601::AID-PROT12&gt;3.0.CO;2-O","article-title":"Crystallization\nand preliminary X-ray analysis of the flavoenzyme vanillyl-alcohol\noxidase from Penicillium simplicissimum","volume":"27","author":"Mattevi","year":"1997","journal-title":"Proteins"},{"issue":"7","key":"2026090306411055600_cit40","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S0969-2126(98)00089-6","article-title":"Protein\nfolds and functions","volume":"6","author":"Martin","year":"1998","journal-title":"Structure"},{"key":"2026090306411055600_cit41","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev.pharmtox.46.120604.141043","article-title":"Human flavin-containing\nmonooxygenases","volume":"46","author":"Cashman","year":"2006","journal-title":"Annu.\nRev. Pharmacol. Toxicol."},{"issue":"9","key":"2026090306411055600_cit42","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202525568","article-title":"Unexpected\nDual Function of Plant\nYUCCA Enzymes Links Chlorophyll Catabolism to Auxin Homeostasis","volume":"65","author":"Ru\u0308tschlin","year":"2026","journal-title":"Angew. Chem., Int. Ed."},{"issue":"50","key":"2026090306411055600_cit43","doi-asserted-by":"publisher","first-page":"17594","DOI":"10.1021\/ja055750t","article-title":"Characterization\nof kinetics and products of the Baeyer-Villiger oxygenase MtmOIV,\nthe key enzyme of the biosynthetic pathway toward the natural product\nanticancer drug mithramycin from Streptomyces argillaceus","volume":"127","author":"Gibson","year":"2005","journal-title":"J. Am. Chem. Soc."},{"issue":"21","key":"2026090306411055600_cit44","doi-asserted-by":"publisher","first-page":"4476","DOI":"10.1021\/bi8023509","article-title":"Crystal structure\nof Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin\nbiosynthetic pathway","volume":"48","author":"Beam","year":"2009","journal-title":"Biochemistry"},{"issue":"48","key":"2026090306411055600_cit45","doi-asserted-by":"publisher","first-page":"18032","DOI":"10.1021\/ja409520v","article-title":"Flavin-linked\noxidase catalyzes pyrrolizine formation\nof dichloropyrrole-containing polyketide extender unit in chlorizidine\nA","volume":"135","author":"Mantovani","year":"2013","journal-title":"J. Am. Chem. Soc."},{"issue":"8","key":"2026090306411055600_cit46","doi-asserted-by":"publisher","first-page":"2864","DOI":"10.1021\/jacs.6b10586","article-title":"Production of Stealthin\nC Involves an S-N-Type Smiles Rearrangement","volume":"139","author":"Wang","year":"2017","journal-title":"J. Am. Chem. Soc."},{"issue":"13","key":"2026090306411055600_cit47","doi-asserted-by":"publisher","first-page":"5913","DOI":"10.1021\/jacs.9b12736","article-title":"Oxidative Carbon Backbone Rearrangement\nin Rishirilide Biosynthesis","volume":"142","author":"Tsypik","year":"2020","journal-title":"J. Am. Chem. Soc."},{"issue":"27","key":"2026090306411055600_cit48","doi-asserted-by":"publisher","first-page":"10413","DOI":"10.1021\/jacs.1c04996","article-title":"A Flavoprotein Dioxygenase Steers Bacterial Tropone\nBiosynthesis via Coenzyme A-Ester Oxygenolysis and Ring Epoxidation","volume":"143","author":"Duan","year":"2021","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026090306411055600_cit49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33131-0","article-title":"Biochemical and structural\ninsights of multifunctional flavin-dependent\nmonooxygenase FlsO1-catalyzed unexpected xanthone formation","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"key":"2026090306411055600_cit50","doi-asserted-by":"publisher","first-page":"5722","DOI":"10.1021\/jacs.5c21759","article-title":"A Hooker Oxygenase\nArchetype in Polyketide Biosynthesis Challenging the Baeyer-Villiger\nMonooxygenase Paradigm","volume":"148","author":"Weddeling","year":"2026","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026090306411055600_cit51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21432-9","article-title":"Enzymatic spiroketal formation via\noxidative rearrangement\nof pentangular polyketides","volume":"12","author":"Frensch","year":"2021","journal-title":"Nat. Commun."},{"key":"2026090306411055600_cit52","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107712","article-title":"Flavoprotein\nmonooxygenases: Versatile biocatalysts","volume":"51","author":"Paul","year":"2021","journal-title":"Biotechnol.\nAdv."},{"issue":"1\u20132","key":"2026090306411055600_cit53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.abb.2010.02.007","article-title":"The FMN-dependent\ntwo-component monooxygenase systems","volume":"497","author":"Ellis","year":"2010","journal-title":"Arch. Biochem.\nBiophys."},{"issue":"47","key":"2026090306411055600_cit54","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202512568","article-title":"Studies of alpha\u2019,beta\u2019-Epoxyketone\nSynthesis\nby Small-Molecule Flavins and Flavoenzymes","volume":"64","author":"Walter","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"issue":"13","key":"2026090306411055600_cit55","doi-asserted-by":"publisher","first-page":"4342","DOI":"10.1021\/jacs.6b01619","article-title":"A Flavin-Dependent Decarboxylase-Dehydrogenase-Monooxygenase\nAssembles the Warhead of alpha,beta-Epoxyketone Proteasome Inhibitors","volume":"138","author":"Zabala","year":"2016","journal-title":"J. Am. Chem. Soc."},{"issue":"9","key":"2026090306411055600_cit56","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1002\/cbic.201500567","article-title":"Epoxomicin\nand Eponemycin Biosynthesis Involves gem-Dimethylation and an Acyl-CoA\nDehydrogenase-Like Enzyme","volume":"17","author":"Zettler","year":"2016","journal-title":"Chembiochem"},{"issue":"4","key":"2026090306411055600_cit57","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.jbiotec.2006.03.044","article-title":"Flavoprotein monooxygenases,\na diverse class of oxidative biocatalysts","volume":"124","author":"van Berkel","year":"2006","journal-title":"J.\nBiotechnol."},{"issue":"12","key":"2026090306411055600_cit58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105413","article-title":"Unifying and versatile features of\nflavin-dependent\nmonooxygenases: Diverse catalysis by a common C4a-(hydro)peroxyflavin","volume":"299","author":"Phintha","year":"2023","journal-title":"J. Biol. Chem."},{"issue":"7","key":"2026090306411055600_cit59","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1096\/fasebj.9.7.7737455","article-title":"Structure\nand mechanism of para-hydroxybenzoate hydroxylase","volume":"9","author":"Entsch","year":"1995","journal-title":"FASEB J."},{"issue":"5182","key":"2026090306411055600_cit60","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1126\/science.7939628","article-title":"The mobile flavin\nof 4-OH benzoate\nhydroxylase","volume":"266","author":"Gatti","year":"1994","journal-title":"Science"},{"issue":"9","key":"2026090306411055600_cit61","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1016\/S0021-9258(17)33523-8","article-title":"Flavin-oxygen\nderivatives involved\nin hydroxylation by p-hydroxybenzoate hydroxylase","volume":"251","author":"Entsch","year":"1976","journal-title":"J. Biol. 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