{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T02:09:25Z","timestamp":1783822165057,"version":"3.55.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1-2","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003484","name":"Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003484","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biol Inorg Chem"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic analyses have identified biallelic variants in the\n                    <jats:italic>4-hydroxyphenylpyruvate dioxygenase-like<\/jats:italic>\n                    (\n                    <jats:italic>HPDL<\/jats:italic>\n                    ) gene as the cause of a neurodegenerative disease that resembles the primary coenzyme Q10 (CoQ10) deficiency syndromes. HPDL is structurally similar to the well-studied 4-hydroxyphenyl pyruvate dioxygenase (HPPD), an iron(II)\/\u03b1-ketoacid-dependent enzyme. HPPD is known to catalyze the second step in the tyrosine metabolism, the oxidative conversion of 4-hydroxyphenylpyruvate (4-HPP) to homogentisic acid (HGA). Hereditary HPPD deficiencies result in high blood tyrosine levels (tyrosinemia type III), which are associated with neurological symptoms such as mental retardation and ataxia. In 2021, 4-hydroxymandelate (4-HMA) was identified as the long-sought intermediate of the biosynthetic pathway from tyrosine to CoQ10. CoQ10 is an important electron shuttle needed in mitochondria for ATP production. Interestingly, HPDL was shown to be able to catalyze the oxygen-dependent reaction of 4-HPP to 4-HMA. Both 4-HPA and 4-HBz occur in the CoQ10 biosynthetic pathway of mammals. CoQ10 has been suspected to be necessary for correct neuronal function, a link to the neurodegenerative HPDL variants. Here, we present a bioinorganic model that can mimic this potential role of HPDL in the conversion of 4-hydroxyphenylpyruvic acid (4-HPA) to 4-hydroxybenzaldehyde (4-HBz). We used fully synthetic iron(III)-hydroxido and iron(IV)-oxido complexes with a ligand of the pentapyridyl-type to study the interconversion of 4-HPA to 4-HBz from a bioinorganic point of view. We show that while an iron(IV)-oxido species, as it occurs in HPPD, is capable of performing the first reaction step from 4-HPA to 4-HMA, an iron(III)-hydroxido species is capable of the transformation of 4-HMA to 4-HBz.\n                  <\/jats:p>","DOI":"10.1007\/s00775-026-02137-0","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T11:51:50Z","timestamp":1773143510000},"page":"91-99","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A bioinorganic view on the potential chemical space of hydroxyphenylpyruvate dioxygenase-like (HPDL) enzymes"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-6164","authenticated-orcid":false,"given":"Niko S. W.","family":"Lindlar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Stucka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-3328","authenticated-orcid":false,"given":"Sophie M.","family":"Gutenthaler-Tietze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-7115","authenticated-orcid":false,"given":"Jonathan","family":"Gutenthaler-Tietze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Senderek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-136X","authenticated-orcid":false,"given":"Lena J.","family":"Daumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"#cr-split#-2137_CR1.1","doi-asserted-by":"crossref","unstructured":"a) EL, Hegg L, Que EJ (1997) Biochem. 250, 625","DOI":"10.1111\/j.1432-1033.1997.t01-1-00625.x"},{"key":"#cr-split#-2137_CR1.2","doi-asserted-by":"crossref","unstructured":"b) I. J. Clifton, M. A. McDonough, D. Ehrismann, N. J. Kershaw, N. Granatino, C. J. Schofield, J. Inorg. Biochem. 2006, 100, 644","DOI":"10.1016\/j.jinorgbio.2006.01.024"},{"key":"2137_CR2","doi-asserted-by":"publisher","first-page":"7694","DOI":"10.1021\/bi2009344","volume":"50","author":"DD Shah","year":"2011","unstructured":"Shah DD, Conrad JA, Heinz B, Brownlee JM, Moran GR (2011) Biochem 50:7694","journal-title":"Biochem"},{"key":"2137_CR3","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1146\/annurev-biochem-061516-044724","volume":"87","author":"MS Islam","year":"2018","unstructured":"Islam MS, Leissing TM, Chowdhury R, Hopkinson RJ, Schofield CJ (2018) Annu Rev Biochem 87:585","journal-title":"Annu Rev Biochem"},{"key":"2137_CR4","doi-asserted-by":"publisher","first-page":"101349","DOI":"10.1016\/j.gim.2024.101349","volume":"27","author":"JE Alecu","year":"2025","unstructured":"Alecu JE, Tam A, Richter S, Quiroz V, Schierbaum L, Saffari A, Ebrahimi-Fakhari D (2025) Genet Med 27:101349","journal-title":"Genet Med"},{"key":"#cr-split#-2137_CR5.1","doi-asserted-by":"crossref","unstructured":"a) I, Micule B, Lace NT, Wright N, Chrestian J, Strautmanis M, Diriks J, Stavusis D, Kidere E, Kleina A, Zdanovica et al (2022) Front. Genet. 13, 780764","DOI":"10.3389\/fgene.2022.780764"},{"key":"#cr-split#-2137_CR5.2","doi-asserted-by":"crossref","unstructured":"b) R. A. Husain, M. Grimmel, M. Wagner, J. C. Hennings, C. Marx, R. G. Feichtinger, A. Saadi, K. Rost\u00e1sy, F. Radelfahr, A. Bevot ., Am. J. Hum. Gen. 2020, 107, 364","DOI":"10.1016\/j.ajhg.2020.06.015"},{"key":"2137_CR6","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1093\/brain\/awab041","volume":"144","author":"M Wiessner","year":"2021","unstructured":"Wiessner M, Maroofian R, Ni M-Y, Pedroni A, M\u00fcller JS, Stucka R, Beetz C, Efthymiou S, Santorelli FM, Alfares AA et al (2021) Brain 144:1422","journal-title":"Brain"},{"key":"2137_CR7","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41586-021-03865-w","volume":"597","author":"RS Banh","year":"2021","unstructured":"Banh RS, Kim ES, Spillier Q, Biancur DE, Yamamoto K, Sohn ASW, Shi G, Jones DR, Kimmelman AC, Pacold ME (2021) Nature 597:420","journal-title":"Nature"},{"key":"2137_CR8","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41586-025-09246-x","volume":"645","author":"G Shi","year":"2025","unstructured":"Shi G, Miller C, Kuno S, Rey Hipolito AG, El Nagar S, Riboldi GM, Korn M, Tran WC, Wang Z, Ficaro L et al (2025) Nature 645:466","journal-title":"Nature"},{"key":"2137_CR9","first-page":"95","volume":"38","author":"JB Dietrich","year":"1992","unstructured":"Dietrich JB (1992) Mol Cell Biol 38:95","journal-title":"Mol Cell Biol"},{"key":"2137_CR10","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1042\/bj0490686","volume":"49","author":"WE Knox","year":"1951","unstructured":"KNOX WE, LeMAY-KNOX M (1951) Biochem J 49:686","journal-title":"Biochem J"},{"key":"#cr-split#-2137_CR11.1","doi-asserted-by":"crossref","unstructured":"a) OW, Choroba DH, Williams JB, Spencer (2000) 122, 5389","DOI":"10.1021\/ja000076v"},{"key":"#cr-split#-2137_CR11.2","doi-asserted-by":"crossref","unstructured":"b) B. K. Hubbard, M. G. Thomas, C. T. Walsh, Chem. Biol. 2000, 7, 931","DOI":"10.1016\/S1074-5521(00)00043-0"},{"key":"2137_CR12","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.tibs.2022.12.006","volume":"48","author":"RM Guerra","year":"2023","unstructured":"Guerra RM, Pagliarini DJ (2023) Trends Biochem Sci 48:463","journal-title":"Trends Biochem Sci"},{"key":"2137_CR13","doi-asserted-by":"publisher","first-page":"30661","DOI":"10.1074\/jbc.M303190200","volume":"278","author":"F Pojer","year":"2003","unstructured":"Pojer F, Kahlich R, Kammerer B, Li S-M, Heide L (2003) J Biol Chem 278:30661","journal-title":"J Biol Chem"},{"key":"2137_CR14","doi-asserted-by":"publisher","unstructured":"Oxidative decarboxylation of \u03b1-hydroxy acids by a functional model of the nonheme iron oxygenase, CloR; Paine, Paria andQue, Chem Comm 2010. https:\/\/doi.org\/10.1039\/B925389K","DOI":"10.1039\/B925389K"},{"key":"2137_CR15","doi-asserted-by":"publisher","first-page":"12091","DOI":"10.1002\/chem.201902340","volume":"25","author":"NSW Jonasson","year":"2019","unstructured":"Jonasson NSW, Daumann LJ (2019) Chem Eur J 25:12091","journal-title":"Chem Eur J"},{"key":"2137_CR16","doi-asserted-by":"publisher","first-page":"21457","DOI":"10.1002\/anie.202107277","volume":"60","author":"D Schmidl","year":"2021","unstructured":"Schmidl D, Jonasson NSW, Korytiakov\u00e1 E, Carell T, Daumann LJ (2021) Angew Chem Int Ed 60:21457","journal-title":"Angew Chem Int Ed"},{"key":"2137_CR17","doi-asserted-by":"publisher","first-page":"3333","DOI":"10.1002\/cbic.202100420","volume":"22","author":"NSW Jonasson","year":"2021","unstructured":"Jonasson N. S. W., Jan\u00dfen R, Menke A, Zott FL, Zipse H, Daumann LJ (2021) ChemBioChem 22:3333","journal-title":"ChemBioChem"},{"key":"2137_CR18","doi-asserted-by":"publisher","first-page":"3719","DOI":"10.1021\/acs.inorgchem.4c04518","volume":"64","author":"NSW Lindlar N\u00e9","year":"2025","unstructured":"Lindlar N\u00e9 NSW, Jonasson A, Menke L, Senft A, Squarcina D, Schmidl K, Fisher S, Demeshko JC, Kruse T, Josephy P, Mayer et al (2025) Inorg Chem 64:3719","journal-title":"Inorg Chem"},{"key":"2137_CR19","doi-asserted-by":"publisher","unstructured":"Dioxygen activation and two consecutive oxidative decarboxylations of phenylpyruvate by nonheme iron(ii) complexes: functional models of hydroxymandelate synthase (HMS) and CloR, Sheet, Bhattacharya and Paine, 2015. Chem. Comm https:\/\/doi.org\/10.1039\/C5CC01652E","DOI":"10.1039\/C5CC01652E"},{"key":"2137_CR20","doi-asserted-by":"publisher","first-page":"5879","DOI":"10.1021\/acs.inorgchem.5b00658","volume":"54","author":"T Chantarojsiri","year":"2015","unstructured":"Chantarojsiri T, Sun Y, Long JR, Chang CJ (2015) Inorg Chem 54:5879","journal-title":"Inorg Chem"},{"key":"2137_CR21","unstructured":"Levin I (2020) NIST inorganic crystal structure database (ICSD). National Institute of Standards and Technology"}],"container-title":["JBIC Journal of Biological Inorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00775-026-02137-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00775-026-02137-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00775-026-02137-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T15:17:47Z","timestamp":1779463067000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00775-026-02137-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":24,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["2137"],"URL":"https:\/\/doi.org\/10.1007\/s00775-026-02137-0","relation":{},"ISSN":["1432-1327"],"issn-type":[{"value":"1432-1327","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"23 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised due to incorrect tagging and affiliation . Now, it has been updated.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}