{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T14:05:25Z","timestamp":1770300325532,"version":"3.49.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302609"],"award-info":[{"award-number":["82302609"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32222006"],"award-info":[{"award-number":["32222006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373781"],"award-info":[{"award-number":["82373781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20230840"],"award-info":[{"award-number":["BK20230840"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds","award":["zdyyxy10"],"award-info":[{"award-number":["zdyyxy10"]}]},{"name":"Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds","award":["zdlyg09"],"award-info":[{"award-number":["zdlyg09"]}]},{"name":"Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit","award":["JSDW202240"],"award-info":[{"award-number":["JSDW202240"]}]},{"name":"the Jiangsu Provincial Key Laboratory of Critical Care Medicine","award":["JSKLCCM202202015"],"award-info":[{"award-number":["JSKLCCM202202015"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Transfusion safety and blood typing continue to present significant challenges in clinical practice, including risks of incorrect blood transfusions and blood shortages. One promising solution is the enzymatic conversion of all red blood cell (RBC) types into universal O-type RBCs. However, the major obstacle to this strategy is the relatively low catalytic efficiency of the enzymes involved. In this study, we investigated two enzymes from <jats:italic>Flavonifractor plautii<\/jats:italic>, N-acetylgalactosamine deacetylase (<jats:italic>Fp<\/jats:italic>GalNAcDeAc) and galactosaminidase (<jats:italic>Fp<\/jats:italic>GalNase), which demonstrate synergistic activity in efficiently converting A-type RBCs to O-type. We optimized treatment conditions, achieving over 99% conversion in just five minutes using phosphate buffer saline and a 16 nM enzyme concentration. Additionally, we engineered two fusion proteins, <jats:italic>Fp<\/jats:italic>GalNAcDeAc-<jats:italic>Fp<\/jats:italic>GalNase and <jats:italic>Fp<\/jats:italic>GalNase-<jats:italic>Fp<\/jats:italic>GalNAcDeAc, which showed a 28-fold increase in catalytic efficiency compared to the enzyme mixture. Using cryo-electron microscopy, we resolved the full-length structure of <jats:italic>Fp<\/jats:italic>GalNase, identifying critical active site residues involved in its catalytic mechanism. This study provides essential structural and biochemical insights for clinical applications in blood group conversion, offering a promising approach for producing universal O-type RBCs.<\/jats:p>","DOI":"10.1186\/s40164-025-00599-7","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T14:09:08Z","timestamp":1737727748000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structural basis of FpGalNase and its combination with FpGalNAcDeAc for efficient A-to-O blood group conversion"],"prefix":"10.1186","volume":"14","author":[{"given":"Meiling","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaishan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuyan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"599_CR1","unstructured":"Blood safety and availability. World Health Organization.  www.whoint\/news-room\/fact-sheets\/detail\/blood-safety-and-availability."},{"issue":"1","key":"599_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.tracli.2003.12.002","volume":"11","author":"ML Olsson","year":"2004","unstructured":"Olsson ML, Hill CA, de la Vega H, Liu QP, Stroud MR, Valdinocci J, Moon S, Clausen H, Kruskall MS. Universal red blood cells\u2013enzymatic conversion of blood group A and B antigens. Transfus Clin Biol. 2004;11(1):33\u20139.","journal-title":"Transfus Clin Biol"},{"issue":"3","key":"599_CR3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1423-0410.1986.tb01946.x","volume":"51","author":"R Oriol","year":"1986","unstructured":"Oriol R, Le Pendu J, Mollicone R. Genetics of ABO, H, Lewis, X and related antigens. Vox Sang. 1986;51(3):161\u201371.","journal-title":"Vox Sang"},{"issue":"4","key":"599_CR4","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/nbt1298","volume":"25","author":"QYP Liu","year":"2007","unstructured":"Liu QYP, Sulzenbacher G, Yuan HP, Bennett EP, Pietz G, Saunders K, Spence J, Nudelman E, Levery SB, White T, et al. Bacterial glycosidases for the production of universal red blood cells. Nat Biotechnol. 2007;25(4):454\u201364.","journal-title":"Nat Biotechnol"},{"issue":"4529","key":"599_CR5","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1126\/science.6274021","volume":"215","author":"J Goldstein","year":"1982","unstructured":"Goldstein J, Siviglia G, Hurst R, Lenny L, Reich L. Group B erythrocytes enzymatically converted to group O survive normally in a, B, and O individuals. 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Nat Microbiol. 2024;9(5):1176-1188.","DOI":"10.1038\/s41564-024-01663-4"},{"issue":"9","key":"599_CR8","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41564-019-0469-7","volume":"4","author":"P Rahfeld","year":"2019","unstructured":"Rahfeld P, Sim L, Moon H, Constantinescu I, Morgan-Lang C, Hallam SJ, Kizhakkedathu JN, Withers SG. An enzymatic pathway in the human gut microbiome that converts a to universal O type blood. Nat Microbiol. 2019;4(9):1475\u201385.","journal-title":"Nat Microbiol"},{"issue":"1","key":"599_CR9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/cbic.201800394","volume":"20","author":"FS Aalbers","year":"2019","unstructured":"Aalbers FS, Fraaije MW. Enzyme fusions in biocatalysis: coupling reactions by pairing enzymes. 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