{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:59:52Z","timestamp":1790837992951,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP210103970"],"award-info":[{"award-number":["DP210103970"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cytochrome P450 enzymes form a large superfamily of monooxygenases capable of oxidising diverse substrates. Among them, members of the CYP108 family are recognised for their role in monoterpenoid oxidation. In this study, we report the identification and characterisation of a new CYP108 family member, CYP108D18, from a metagenome\u2010assembled genome derived from microbial communities in a geothermal hot spring located in northern Queensland, Australia. Taxonomic binning associated CYP108D18 with a\n                    <jats:italic>Novosphingobium<\/jats:italic>\n                    species, a genus well\u2010known for its bioremediation potential. CYP108D18 was heterologously expressed in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                    <\/jats:styled-content>\n                    , yielding 640\u2009nmol\u2009L\n                    <jats:sup>\u22121<\/jats:sup>\n                    of culture, and purified to homogeneity. The enzyme exhibited moderate thermostability, with a\n                    <jats:sup>15<\/jats:sup>\n                    T\n                    <jats:sub>50<\/jats:sub>\n                    value of 47\u00b0C\u2009\u00b1\u20091\u00b0C. Spectroscopic substrate binding assays revealed that while CYP108D18 bound monoterpenoids similarly to other CYP108 enzymes, it showed higher affinity and pronounced larger heme spin\u2010state shifts with aromatic hydrocarbons such as phenylcyclohexane and phenanthrene. Subsequent in silico docking and spectral\u2010binding studies also suggested that CYP108D18 may accommodate larger plant\u2010derived sesquiterpenes, indicating a potential role in their metabolism. Reconstitution of CYP108D18 with spinach ferredoxin and ferredoxin reductase resulted in the oxidation of phenylcyclohexane to\n                    <jats:italic>trans<\/jats:italic>\n                    \u20104\u2010phenylcyclohexanol. Molecular dynamics simulations and ONIOM (QM\/MM) calculations supported selective hydrogen abstraction at the cyclohexane C4 position, rationalising\n                    <jats:italic>trans<\/jats:italic>\n                    \u20104\u2010phenylcyclohexanol as the predominant product. The high\u2010resolution crystal structure of substrate\u2010free CYP108D18 revealed a bound dioxygen ligand positioned above the heme iron, an unusual feature among P450 structures. Both substrate\u2010free and phenylcyclohexane\u2010bound structures revealed a persistent open conformation, suggesting the absence of a canonical open\u2010to\u2010closed transition upon ligand binding. Spectroelectrochemical analysis showed a heme redox potential of \u2212451\u2009mV versus NHE for the substrate\u2010free CYP108D18, shifting subtly to \u2212409\u2009mV upon phenylcyclohexane binding, which contributes to reduced activity with non\u2010native [2Fe\u20102S] ferredoxins.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70451","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:42:43Z","timestamp":1790836963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural and Functional Characterisation of a Metagenome\u2010Derived\n                    <scp>CYP108D18<\/scp>\n                    Reveals an Unusual Dioxygen\u2010Bound State and Selective Hydrocarbon Hydroxylation"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-9016","authenticated-orcid":false,"given":"Simran","family":"Kundral","sequence":"first","affiliation":[{"name":"The University of Queensland \u2010 Indian Institute of Technology Delhi (UQIITD) Research Academy  New Delhi India"},{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"},{"name":"Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry Indian Institute of Technology Delhi  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1408-997X","authenticated-orcid":false,"given":"Peter D.","family":"Giang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-5274","authenticated-orcid":false,"given":"Alicia M.","family":"Kirk","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"},{"name":"Scuola Normale Superiore  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9753-7207","authenticated-orcid":false,"given":"Julia B.","family":"Buczynski","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-2718","authenticated-orcid":false,"given":"Kasun S. A.","family":"Arachchige","sequence":"additional","affiliation":[{"name":"Centre for Microscopy and Microanalysis The University of Queensland  St. Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-3058","authenticated-orcid":false,"given":"Sunil K.","family":"Khare","sequence":"additional","affiliation":[{"name":"Enzyme and Microbial Biochemistry Laboratory, Department of Chemistry Indian Institute of Technology Delhi  New Delhi India"},{"name":"Department of Biological Sciences Indian Institute of Science Education and Research Kolkata  Mohanpur West Bengal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-1763","authenticated-orcid":false,"given":"Paul V.","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-2602","authenticated-orcid":false,"given":"Paul N.","family":"Evans","sequence":"additional","affiliation":[{"name":"Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8204-8408","authenticated-orcid":false,"given":"Luke W.","family":"Guddat","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-9727","authenticated-orcid":false,"given":"Stephen G.","family":"Bell","sequence":"additional","affiliation":[{"name":"School of Physics, Chemistry and Earth Sciences Adelaide University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-5140","authenticated-orcid":false,"given":"James J.","family":"De Voss","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences The University of Queensland  St Lucia Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions With AlphaFold 3","volume":"630","author":"Abramson J.","year":"2024","journal-title":"Nature"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: A Comprehensive Python\u2010Based System for Macromolecular Structure Solution","volume":"66","author":"Adams P. 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