{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:28:07Z","timestamp":1787372887889,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007316","name":"Klaus Tschira Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007316","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/052jep661","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012688","name":"University of Rostock","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012688","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03zdwsf69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Landesgraduiertenfoerderung Mecklenburg-Vorpommern"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Streptococcus cristatus (S. cristatus) belongs to the viridans group of streptococci and is a commensal of the human upper respiratory tract. With the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase, GapN, and the oxidative part of the pentose phosphate pathway (oxPPP), S. cristatus can use two different metabolic pathways to provide reduced nicotinamide adenine dinucleotide phosphate (NADPH), an essential cofactor of anabolic reactions such as fatty acid and amino acid biosynthesis. Regarding their NADP-reducing capacity, streptococci can be categorized into three groups: those that have only GapN, those that use only the oxPPP, and those that use both pathways. Here, we report on the experimental and computational characterization of the catalytic properties of the three NADP-reducing enzymes: GapN, glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH) of S. cristatus. Kinetic analyses showed moderate substrate and cofactor affinities, with GapN displaying the tightest substrate binding, followed by 6PGDH and G6PDH, in agreement with structural and computational predictions. All three enzymes preferentially utilized NADP+, with only G6PDH exhibiting limited NAD+ promiscuity. Growth-phase-dependent activity patterns suggest dynamic adjustment of NADPH-generating pathways, with reduced GapN contribution and sustained oxPPP activity in the stationary phase. Regulatory screening indicated limited allosteric control, though feedback inhibition by NADPH and the ATP sensitivity of G6PDH point to conserved redox regulatory mechanisms. Comparative analysis across streptococci supports the concept that the coexistence of GapN and the oxidative pentose phosphate pathway in S. cristatus may provide metabolic flexibility by offering alternative routes for NADPH generation.<\/jats:p>","DOI":"10.3390\/biom16081212","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T09:48:31Z","timestamp":1787219311000},"page":"1212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Catalytic Properties of NADP-Reducing Enzymes from Streptococcus cristatus ATCC 51100"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3996-7166","authenticated-orcid":false,"given":"Isabell","family":"Sch\u00fctt","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-0804","authenticated-orcid":false,"given":"Jonathan","family":"Teuffel","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies, 69118 Heidelberg, Germany"},{"name":"Center for Molecular Biology of Heidelberg University (ZMBH), German Cancer Research Center (DKFZ)-ZMBH Alliance, 69117 Heidelberg, Germany"},{"name":"Graduate School of Mathematical and Computational Methods for the Sciences (HGS MathComp), Heidelberg University, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben H.","family":"Hlawatschke","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-6578","authenticated-orcid":false,"given":"Philip","family":"Einwohlt","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9527-5098","authenticated-orcid":false,"given":"Bernd","family":"Kreikemeyer","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5951-8670","authenticated-orcid":false,"given":"Rebecca C.","family":"Wade","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies, 69118 Heidelberg, Germany"},{"name":"Center for Molecular Biology of Heidelberg University (ZMBH), German Cancer Research Center (DKFZ)-ZMBH Alliance, 69117 Heidelberg, Germany"},{"name":"Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, 69117 Heidelberg, Germany"},{"name":"Faculty of Engineering Sciences, Heidelberg University, 69117 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-1865","authenticated-orcid":false,"given":"Tomas","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, Virology, and Hygiene, Rostock University Medical Centre, Schillingallee 70, 18057 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1113\/expphysiol.1997.sp004024","article-title":"Oxidative stress: Oxidants and antioxidants","volume":"82","author":"Sies","year":"1997","journal-title":"Exp. 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