{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:04Z","timestamp":1792785964562,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004155","name":"Magnus Ehrnrooth Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004785","name":"NordForsk","doi-asserted-by":"publisher","award":["82845"],"award-info":[{"award-number":["82845"]}],"id":[{"id":"10.13039\/501100004785","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Doctoral Program in Microbiology and Biotechnology of the University of Helsinki","id":[{"id":"https:\/\/ror.org\/040af2s02","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF22OC0080109"],"award-info":[{"award-number":["NNF22OC0080109"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Aberrant activity of human trypsin isoenzymes has been linked to diseases like cancer. The high structural and catalytic similarity among the three human trypsin isoenzymes makes selective inhibition of individual trypsin isoenzymes particularly challenging. As cyanobacteria are a prolific source of structurally diverse serine protease inhibitors with potential pharmaceutical applications, we studied them as producers of selective human trypsin inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Here, we evaluated aqueous extracts of 505 strains of cyanobacteria, isolated from the Baltic Sea and Finnish lakes, for inhibitory activity against human trypsin isoenzymes. Extracts from 98 strains (19% of those tested), belonging primarily to the genera Microcystis, Nodularia, Nostoc, Oscillatoria, and Planktothrix, exhibited inhibitory activity against one or more trypsin isoenzymes. Twenty-four extracts preferentially inhibited trypsin-1 and trypsin-2, eight inhibited both trypsin-2 and trypsin-3, and seven showed selectivity toward trypsin-2 alone. We selected eight extracts for further bioactivity tests against plasma-KLK, bovine trypsin, Factor Xa, and thrombin. While all of these extracts inhibited bovine trypsin, some also inhibited plasma-KLK, thrombin, or Factor Xa. Molecular networking of high-resolution mass spectrometry data indicated the presence of both known trypsin inhibitors and potentially novel metabolites, suggesting that cyanobacteria represent a rich source of natural products with selective activity against human trypsin isoenzymes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, these results suggest that cyanobacteria harbor a wealth of metabolites with selective inhibitory activity against human trypsin isoenzymes that could serve as a starting point for the development of protease inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jambio\/lxag167","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:41:46Z","timestamp":1783424506000},"source":"Crossref","is-referenced-by-count":0,"title":["Selective human trypsin inhibitors from cyanobacteria"],"prefix":"10.1093","volume":"137","author":[{"given":"Xiaodan","family":"Ouyang","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Haematology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital , P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad N","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Haematology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital , P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki ,","place":["Finland"]},{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Wahlsten","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania K","family":"Shishido","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]},{"name":"Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki , Viikinkaari 5D, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jouni","family":"Jokela","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaarina","family":"Sivonen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Fewer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki , P.O. Box 56, Viikinkaari 9, Biocenter 1, FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0926-3109","authenticated-orcid":false,"given":"Hannu","family":"Koistinen","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Haematology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital , P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"2026092506425712200_bib1","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1021\/acschembio.1c00611","article-title":"Potent inhibitor of human trypsins from the aeruginosin family of natural products","volume":"16","author":"Ahmed","year":"2021","journal-title":"ACS Chem Biol"},{"key":"2026092506425712200_bib2","doi-asserted-by":"publisher","first-page":"21523","DOI":"10.1074\/jbc.M115.662429","article-title":"Mesotrypsin has evolved four unique residues to cleave trypsin inhibitors as aubstrates","volume":"290","author":"Alloy","year":"2015","journal-title":"J Biol Chem"},{"key":"2026092506425712200_bib3","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1074\/jbc.TM118.004156","article-title":"Proteases: history, discovery, and roles in health 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