{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:51:26Z","timestamp":1791255086683,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM147387"],"award-info":[{"award-number":["R35GM147387"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","award":["763955"],"award-info":[{"award-number":["763955"]}],"id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR-1720256"],"award-info":[{"award-number":["DMR-1720256"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE-2247505"],"award-info":[{"award-number":["CHE-2247505"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Synth"],"DOI":"10.1038\/s44160-024-00536-2","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T10:03:04Z","timestamp":1714125784000},"page":"967-975","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Biocatalytic enantioselective C(sp3)\u2013H fluorination enabled by directed evolution of non-haem iron enzymes"],"prefix":"10.1038","volume":"3","author":[{"given":"Liu-Peng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8487-1417","authenticated-orcid":false,"given":"Binh Khanh","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangqiu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0330-6885","authenticated-orcid":false,"given":"Yunlong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4593-1629","authenticated-orcid":false,"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7590","authenticated-orcid":false,"given":"Yongda","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-632X","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-2034","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"536_CR1","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1002\/anie.201409470","volume":"54","author":"H Renata","year":"2015","unstructured":"Renata, H., Wang, Z. J. & Arnold, F. H. Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution. Angew. Chem. Int. Ed. 54, 3351\u20133367 (2015).","journal-title":"Angew. Chem. Int. Ed."},{"key":"536_CR2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.copbio.2017.06.005","volume":"47","author":"OF Brandenberg","year":"2017","unstructured":"Brandenberg, O. F., Fasan, R. & Arnold, F. H. Exploiting and engineering hemoproteins for abiological carbene and nitrene transfer reactions. Curr. Opin. Biotechnol. 47, 102\u2013111 (2017).","journal-title":"Curr. Opin. Biotechnol."},{"key":"536_CR3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41570-019-0143-x","volume":"3","author":"RB Leveson-Gower","year":"2019","unstructured":"Leveson-Gower, R. B., Mayer, C. & Roelfes, G. The importance of catalytic promiscuity for enzyme design and evolution. Nat. Rev. Chem. 3, 687\u2013705 (2019).","journal-title":"Nat. Rev. Chem."},{"key":"536_CR4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41929-019-0385-5","volume":"3","author":"K Chen","year":"2020","unstructured":"Chen, K. & Arnold, F. H. Engineering new catalytic activities in enzymes. Nat. Catal. 3, 203\u2013213 (2020).","journal-title":"Nat. Catal."},{"key":"536_CR5","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.trechm.2022.03.002","volume":"4","author":"C Klaus","year":"2022","unstructured":"Klaus, C. & Hammer, S. C. New catalytic reactions by enzyme engineering. Trends Chem. 4, 363\u2013366 (2022).","journal-title":"Trends Chem."},{"key":"536_CR6","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1126\/science.abk1603","volume":"374","author":"Q Zhou","year":"2021","unstructured":"Zhou, Q., Chin, M., Fu, Y., Liu, P. & Yang, Y. Stereodivergent atom-transfer radical cyclization by engineered cytochromes P450. Science 374, 1612\u2013P1616 (2021).","journal-title":"Science"},{"key":"536_CR7","doi-asserted-by":"crossref","first-page":"13344","DOI":"10.1021\/jacs.2c04937","volume":"144","author":"Y Fu","year":"2022","unstructured":"Fu, Y. et al. Engineered P450 atom-transfer radical cyclases are bifunctional biocatalysts: reaction mechanism and origin of enantioselectivity. J. Am. Chem. Soc. 144, 13344\u201313355 (2022).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR8","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41929-023-00986-5","volume":"6","author":"W Fu","year":"2023","unstructured":"Fu, W. et al. Enzyme-controlled stereoselective radical cyclization to arenes enabled by metalloredox biocatalysis. Nat. Catal. 6, 628\u2013636 (2023).","journal-title":"Nat. Catal."},{"key":"536_CR9","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1126\/science.abj2830","volume":"376","author":"J Rui","year":"2022","unstructured":"Rui, J. et al. Directed evolution of nonheme iron enzymes to access abiological radical-relay C(sp3)\u2013H azidation. Science 376, 869\u2013874 (2022).","journal-title":"Science"},{"key":"536_CR10","doi-asserted-by":"crossref","first-page":"100494","DOI":"10.1016\/j.cogsc.2021.100494","volume":"31","author":"X Ren","year":"2021","unstructured":"Ren, X. & Fasan, R. Engineered and artificial metalloenzymes for selective C\u2013H functionalization. Curr. Opin. Green Sustain. Chem. 31, 100494 (2021).","journal-title":"Curr. Opin. Green Sustain. Chem."},{"key":"536_CR11","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1021\/acs.chemrev.2c00767","volume":"123","author":"MA Emmanuel","year":"2023","unstructured":"Emmanuel, M. A. et al. Photobiocatalytic strategies for organic synthesis. Chem. Rev. 123, 5459\u20135520 (2023).","journal-title":"Chem. Rev."},{"key":"536_CR12","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1021\/acs.accounts.1c00719","volume":"55","author":"W Harrison","year":"2022","unstructured":"Harrison, W., Huang, X. & Zhao, H. Photobiocatalysis for abiological transformations. Acc. Chem. Res. 55, 1087\u20131096 (2022).","journal-title":"Acc. Chem. Res."},{"key":"536_CR13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1126\/science.adg2420","volume":"381","author":"L Cheng","year":"2023","unstructured":"Cheng, L. et al. Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis. Science 381, 444\u2013451 (2023).","journal-title":"Science"},{"key":"536_CR14","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1021\/cr4002879","volume":"114","author":"J Wang","year":"2014","unstructured":"Wang, J. et al. Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001\u20132011). Chem. Rev. 114, 2432\u20132506 (2014).","journal-title":"Chem. Rev."},{"key":"536_CR15","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.1021\/acs.jmedchem.5b00258","volume":"58","author":"EP Gillis","year":"2015","unstructured":"Gillis, E. P., Eastman, K. J., Hill, M. D., Donnelly, D. J. & Meanwell, N. A. Applications of fluorine in medicinal chemistry. J. Med. Chem. 58, 8315\u20138359 (2015).","journal-title":"J. Med. Chem."},{"key":"536_CR16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1021\/acs.chemrev.5b00392","volume":"116","author":"Y Zhou","year":"2016","unstructured":"Zhou, Y. et al. Next generation of fluorine-containing pharmaceuticals, compounds currently in phase II\u2013III clinical trials of major pharmaceutical companies: new structural trends and therapeutic areas. Chem. Rev. 116, 422\u2013518 (2016).","journal-title":"Chem. Rev."},{"key":"536_CR17","doi-asserted-by":"crossref","first-page":"101467","DOI":"10.1016\/j.isci.2020.101467","volume":"23","author":"Y Ogawa","year":"2020","unstructured":"Ogawa, Y., Tokunaga, E., Kobayashi, O., Hirai, K. & Shibata, N. Current contributions of organofluorine compounds to the agrochemical industry. iScience. 23, 101467 (2020).","journal-title":"iScience."},{"key":"536_CR18","doi-asserted-by":"crossref","first-page":"10633","DOI":"10.1021\/acsomega.0c00830","volume":"5","author":"M Inoue","year":"2020","unstructured":"Inoue, M., Sumii, Y. & Shibata, N. Contribution of organofluorine compounds to pharmaceuticals. ACS Omega 5, 10633\u201310640 (2020).","journal-title":"ACS Omega"},{"key":"536_CR19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.cbpa.2020.01.004","volume":"55","author":"L Wu","year":"2020","unstructured":"Wu, L., Maglangit, F. & Deng, H. Fluorine biocatalysis. Curr. Opin. Chem. Biol. 55, 119\u2013126 (2020).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"536_CR20","doi-asserted-by":"crossref","first-page":"6527","DOI":"10.1039\/C4CS00027G","volume":"43","author":"MC Walker","year":"2014","unstructured":"Walker, M. C. & Chang, M. C. Y. Natural and engineered biosynthesis of fluorinated natural products. Chem. Soc. Rev. 43, 6527\u20136536 (2014).","journal-title":"Chem. Soc. Rev."},{"key":"536_CR21","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1242345","volume":"341","author":"M Walker","year":"2013","unstructured":"Walker, M. et al. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways. Science 341, 1089\u20131094 (2013).","journal-title":"Science"},{"key":"536_CR22","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41589-022-01070-y","volume":"18","author":"S Sirirungruang","year":"2022","unstructured":"Sirirungruang, S. et al. Engineering site-selective incorporation of fluorine into polyketides. Nat. Chem. Biol. 18, 886\u2013893 (2022).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR23","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/s41557-022-00996-z","volume":"14","author":"A Rittner","year":"2022","unstructured":"Rittner, A. et al. Chemoenzymatic synthesis of fluorinated polyketides. Nat. Chem. 14, 1000\u20131006 (2022).","journal-title":"Nat. Chem."},{"key":"536_CR24","doi-asserted-by":"crossref","first-page":"14824","DOI":"10.1002\/anie.201814457","volume":"58","author":"R Szpera","year":"2019","unstructured":"Szpera, R., Moseley, D. F. J., Smith, L. B., Sterling, A. J. & Gouverneur, V. The fluorination of C\u2013H bonds: developments and perspectives. Angew. Chem. Int. Ed. 58, 14824\u201314848 (2019).","journal-title":"Angew. Chem. Int. Ed."},{"key":"536_CR25","doi-asserted-by":"crossref","first-page":"9928","DOI":"10.1021\/jacs.3c01824","volume":"145","author":"IN-M Leibler","year":"2023","unstructured":"Leibler, I. N.-M., Gandhi, S. S., Tekle-Smith, M. A. & Doyle, A. G. Strategies for nucleophilic C(sp3)\u2013(radio)fluorination. J. Am. Chem. Soc. 145, 9928\u20139950 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR26","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1021\/ja5039819","volume":"136","author":"X Huang","year":"2014","unstructured":"Huang, X. et al. Late stage benzylic C\u2013H fluorination with [18F]fluoride for PET imaging. J. Am. Chem. Soc. 136, 6842\u20136845 (2014).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR27","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/s41557-018-0048-1","volume":"10","author":"H Park","year":"2018","unstructured":"Park, H., Verma, P., Hong, K. & Yu, J.-Q. Controlling Pd(IV) reductive elimination pathways enables Pd(II)-catalysed enantioselective C(sp3)\u2013H fluorination. Nat. Chem. 10, 755\u2013762 (2018).","journal-title":"Nat. Chem."},{"key":"536_CR28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s43586-021-00042-1","volume":"1","author":"R Britton","year":"2021","unstructured":"Britton, R. et al. Contemporary synthetic strategies in organofluorine chemistry. Nat. Rev. Methods Primers 1, 47 (2021).","journal-title":"Nat. Rev. Methods Primers"},{"key":"536_CR29","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s00044-023-03094-y","volume":"32","author":"D O\u2019Hagan","year":"2023","unstructured":"O\u2019Hagan, D. & Young, R. J. Future challenges and opportunities with fluorine in drugs? Med. Chem. Res. 32, 1231\u20131234 (2023).","journal-title":"Med. Chem. Res."},{"key":"536_CR30","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1021\/cr500209t","volume":"115","author":"D O\u2019Hagan","year":"2015","unstructured":"O\u2019Hagan, D. & Deng, H. Enzymatic fluorination and biotechnological developments of the fluorinase. Chem. Rev. 115, 634\u2013649 (2015).","journal-title":"Chem. Rev."},{"key":"536_CR31","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1021\/cr050313i","volume":"106","author":"FH Vaillancourt","year":"2006","unstructured":"Vaillancourt, F. H., Yeh, E., Vosburg, D. A., Garneau-Tsodikova, S. & Walsh, C. T. Nature\u2019s inventory of halogenation catalysts: oxidative strategies predominate. Chem. Rev. 106, 3364\u20133378 (2006).","journal-title":"Chem. Rev."},{"key":"536_CR32","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1021\/acs.chemrev.6b00571","volume":"117","author":"V Agarwal","year":"2017","unstructured":"Agarwal, V. et al. Enzymatic halogenation and dehalogenation reactions: pervasive and mechanistically diverse. Chem. Rev. 117, 5619\u20135674 (2017).","journal-title":"Chem. Rev."},{"key":"536_CR33","doi-asserted-by":"crossref","first-page":"9443","DOI":"10.1039\/D0CS01551B","volume":"50","author":"C Crowe","year":"2021","unstructured":"Crowe, C. et al. Halogenases: a palette of emerging opportunities for synthetic biology\u2013synthetic chemistry and C\u2013H functionalisation. Chem. Soc. Rev. 50, 9443\u20139481 (2021).","journal-title":"Chem. Soc. Rev."},{"key":"536_CR34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1021\/acs.biochem.2c00115","volume":"62","author":"A Papadopoulou","year":"2023","unstructured":"Papadopoulou, A., Meyer, F. & Buller, R. M. Engineering Fe(II)\/\u03b1-ketoglutarate-dependent halogenases and desaturases. Biochemistry 62, 229\u2013240 (2023).","journal-title":"Biochemistry"},{"key":"536_CR35","doi-asserted-by":"crossref","first-page":"18535","DOI":"10.1002\/anie.201907245","volume":"58","author":"T Hayashi","year":"2019","unstructured":"Hayashi, T. et al. Evolved aliphatic halogenases enable regiocomplementary C\u2013H functionalization of a pharmaceutically relevant compound. Angew. Chem. Int. Ed. 58, 18535\u201318539 (2019).","journal-title":"Angew. Chem. Int. Ed."},{"key":"536_CR36","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/cbic.200500480","volume":"7","author":"FH Vaillancourt","year":"2006","unstructured":"Vaillancourt, F. H., Vosburg, D. A. & Walsh, C. T. Dichlorination and bromination of a threonyl-S-carrier protein by the non-heme FeII halogenase SyrB2. ChemBioChem 7, 748\u2013752 (2006).","journal-title":"ChemBioChem"},{"key":"536_CR37","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nchembio.1438","volume":"10","author":"ML Matthews","year":"2014","unstructured":"Matthews, M. L. et al. Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase. Nat. Chem. Biol. 10, 209\u2013215 (2014).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR38","doi-asserted-by":"crossref","first-page":"e202301370","DOI":"10.1002\/anie.202301370","volume":"62","author":"CA Gomez","year":"2023","unstructured":"Gomez, C. A., Mondal, D., Du, Q., Chan, N. & Lewis, J. C. Directed evolution of an iron(II)- and \u03b1-ketoglutarate-dependent dioxygenase for site-selective azidation of unactivated aliphatic C\u2013H bonds.Angew. Chem. Int. Ed. 62, e202301370 (2023).","journal-title":"Angew. Chem. Int. Ed."},{"key":"536_CR39","doi-asserted-by":"crossref","first-page":"14477","DOI":"10.1021\/acs.inorgchem.2c02872","volume":"61","author":"NH Chan","year":"2022","unstructured":"Chan, N. H. et al. Non-native anionic ligand binding and reactivity in engineered variants of the Fe(II)- and \u03b1-ketoglutarate-dependent oxygenase, SadA. Inorg. Chem. 61, 14477\u201314485 (2022).","journal-title":"Inorg. Chem."},{"key":"536_CR40","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1021\/jp0311512","volume":"108","author":"C-G Zhan","year":"2004","unstructured":"Zhan, C.-G. & Dixon, D. A. Hydration of the fluoride anion: structures and absolute hydration free energy from first-principles electronic structure calculations. J. Phys. Chem. A 108, 2020\u20132029 (2004).","journal-title":"J. Phys. Chem. A"},{"key":"536_CR41","doi-asserted-by":"crossref","first-page":"12771","DOI":"10.1021\/jacs.6b08171","volume":"138","author":"BJ Groendyke","year":"2016","unstructured":"Groendyke, B. J., AbuSalim, D. I. & Cook, S. P. Iron-catalyzed, fluoroamide-directed C\u2013H fluorination. J. Am. Chem. Soc. 138, 12771\u201312774 (2016).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR42","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1039\/C9SC04055B","volume":"11","author":"EN Pinter","year":"2020","unstructured":"Pinter, E. N., Bingham, J. E., AbuSalim, D. I. & Cook, S. P. N-directed fluorination of unactivated Csp3\u2013H bonds. Chem. Sci. 11, 1102\u20131106 (2020).","journal-title":"Chem. Sci."},{"key":"536_CR43","doi-asserted-by":"crossref","first-page":"10096","DOI":"10.1021\/ja8005397","volume":"130","author":"W Ge","year":"2008","unstructured":"Ge, W. et al. Isopenicillin N synthase mediates thiolate oxidation to sulfenate in a depsipeptide substrate analogue: implications for oxygen binding and a link to nitrile hydratase? J. Am. Chem. Soc. 130, 10096\u201310102 (2008).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR44","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0969-2126(01)00695-5","volume":"10","author":"RC Wilmouth","year":"2002","unstructured":"Wilmouth, R. C. et al. Structure and mechanism of anthocyanidin synthase from Arabidopsis thaliana. Structure 10, 93\u2013103 (2002).","journal-title":"Structure"},{"key":"536_CR45","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1021\/bi0484421","volume":"44","author":"B Gopal","year":"2005","unstructured":"Gopal, B., Madan, L. L., Betz, S. F. & Kossiakoff, A. A. The crystal structure of a quercetin 2,3-dioxygenase from Bacillus subtilis suggests modulation of enzyme activity by a change in the metal ion at the active site(s). Biochemistry 44, 193\u2013201 (2005).","journal-title":"Biochemistry"},{"key":"536_CR46","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.chembiol.2004.08.012","volume":"11","author":"Z Zhang","year":"2004","unstructured":"Zhang, Z., Ren, J.-S., Clifton, I. J. & Schofield, C. J. Crystal structure and mechanistic implications of 1-aminocyclopropane-1-carboxylic acid oxidase\u2014the ethylene-forming enzyme. Chem. Biol. 11, 1383\u20131394 (2004).","journal-title":"Chem. Biol."},{"key":"536_CR47","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3389\/fpls.2019.00695","volume":"10","author":"M Houben","year":"2019","unstructured":"Houben, M. & Van de Poel, B. 1-Aminocyclopropane-1-carboxylic acid oxidase (ACO): the enzyme that makes the plant hormone ethylene. Front. Plant Sci. 10, 695 (2019).","journal-title":"Front. Plant Sci."},{"key":"536_CR48","doi-asserted-by":"crossref","first-page":"10111","DOI":"10.1073\/pnas.0504412102","volume":"102","author":"FH Vaillancourt","year":"2005","unstructured":"Vaillancourt, F. H., Yin, J. & Walsh, C. T. SyrB2 in syringomycin E biosynthesis is a nonheme FeII \u03b1-ketoglutarate- and O2-dependent halogenase. Proc. Natl Acad. Sci. USA 102, 10111\u201310116 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"536_CR49","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature04544","volume":"440","author":"LC Blasiak","year":"2006","unstructured":"Blasiak, L. C., Vaillancourt, F. H., Walsh, C. T. & Drennan, C. L. Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis. Nature 440, 368\u2013371 (2006).","journal-title":"Nature"},{"key":"536_CR50","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/nchembio.2112","volume":"12","author":"AJ Mitchell","year":"2016","unstructured":"Mitchell, A. J. et al. Structural basis for halogenation by iron- and 2-oxo-glutarate-dependent enzyme WelO5. Nat. Chem. Biol. 12, 636\u2013640 (2016).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR51","doi-asserted-by":"crossref","unstructured":"Liu, X. in Methods in Enzymology, Vol. 604 (ed. Moore, B. S.) 389\u2013404 (Academic Press, 2018).","DOI":"10.1016\/bs.mie.2018.02.015"},{"key":"536_CR52","doi-asserted-by":"crossref","first-page":"e202201115","DOI":"10.1002\/cctc.202201115","volume":"14","author":"M Voss","year":"2022","unstructured":"Voss, M. et al. Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*. ChemCatChem 14, e202201115 (2022).","journal-title":"ChemCatChem"},{"key":"536_CR53","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41467-022-27999-1","volume":"13","author":"J B\u00fcchler","year":"2022","unstructured":"B\u00fcchler, J. et al. Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens. Nat. Comm. 13, 371 (2022).","journal-title":"Nat. Comm."},{"key":"536_CR54","doi-asserted-by":"crossref","unstructured":"Duewel, S. et al. Directed evolution of an FeII-dependent halogenase for asymmetric C(sp3)\u2013H chlorination. ACS Catal. 10, 1272\u20131277 (2020).","DOI":"10.1021\/acscatal.9b04691"},{"key":"536_CR55","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/nchembio.1625","volume":"10","author":"ML Hillwig","year":"2014","unstructured":"Hillwig, M. L. & Liu, X. A new family of iron-dependent halogenases acts on freestanding substrates. Nat. Chem. Biol. 10, 921\u2013923 (2014).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR56","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41586-019-1020-y","volume":"567","author":"JA Marchand","year":"2019","unstructured":"Marchand, J. A. et al. Discovery of a pathway for terminal-alkyne amino acid biosynthesis. Nature 567, 420\u2013424 (2019).","journal-title":"Nature"},{"key":"536_CR57","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/s41589-019-0355-x","volume":"15","author":"ME Neugebauer","year":"2019","unstructured":"Neugebauer, M. E. et al. A family of radical halogenases for the engineering of amino-acid-based products. Nat. Chem. Biol. 15, 1009\u20131016 (2019).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR58","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/s41589-021-00944-x","volume":"18","author":"ME Neugebauer","year":"2022","unstructured":"Neugebauer, M. E. et al. Reaction pathway engineering converts a radical hydroxylase into a halogenase. Nat. Chem. Biol. 18, 171\u2013179 (2022).","journal-title":"Nat. Chem. Biol."},{"key":"536_CR59","doi-asserted-by":"crossref","first-page":"7327","DOI":"10.1021\/acscatal.1c00847","volume":"11","author":"A Knorrscheidt","year":"2021","unstructured":"Knorrscheidt, A. et al. Accessing chemo- and regioselective benzylic and aromatic oxidations by protein engineering of an unspecific peroxygenase. ACS Catal. 11, 7327\u20137338 (2021).","journal-title":"ACS Catal."},{"key":"536_CR60","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1021\/ja107339h","volume":"133","author":"D Usharani","year":"2011","unstructured":"Usharani, D., Janardanan, D. & Shaik, S. Does the TauD enzyme always hydroxylate alkanes, while an analogous synthetic non-heme reagent always desaturates them? J. Am. Chem. Soc. 133, 176\u2013179 (2011).","journal-title":"J. Am. Chem. Soc."},{"key":"536_CR61","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1021\/acs.macromol.6b02286","volume":"50","author":"S Lanzalaco","year":"2017","unstructured":"Lanzalaco, S. et al. Atom transfer radical polymerization with different halides (F, Cl, Br, and I): is the process \u2018living\u2019 in the presence of fluorinated initiators? Macromolecules 50, 192\u2013202 (2017).","journal-title":"Macromolecules"},{"key":"536_CR62","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1021\/acs.jctc.7b00688","volume":"13","author":"YA Aoto","year":"2017","unstructured":"Aoto, Y. A., de Lima Batista, A. P., Kohn, A. & de Oliveira-Filho, A. G. S. How to arrive at accurate benchmark values for transition metal compounds: computation or experiment? J. Chem. Theory Comput. 13, 5291\u20135316 (2017).","journal-title":"J. Chem. Theory Comput."}],"container-title":["Nature Synthesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44160-024-00536-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44160-024-00536-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44160-024-00536-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T15:13:46Z","timestamp":1723475626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44160-024-00536-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":62,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["536"],"URL":"https:\/\/doi.org\/10.1038\/s44160-024-00536-2","relation":{},"ISSN":["2731-0582"],"issn-type":[{"value":"2731-0582","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]},"assertion":[{"value":"25 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}