{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:48:45Z","timestamp":1760147325001,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Foundation for Science and Technology (Portugal)","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"CY-SENSORS","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"COMPETE 2020","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"Portugal 2020","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"European Union","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]},{"name":"ERDF","award":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["PTDC\/BTA-GES\/32359\/2017","UIDB\/04423\/2020","UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Cyanobacteria produce a wealth of secondary metabolites. Since these organisms attach fatty acids into molecules in unprecedented ways, cyanobacteria can serve as a novel source for bioactive compounds acting as ligands for Peroxisome Proliferator-Activated Receptors (PPAR). PPARs (PPAR\u03b1, PPAR\u03b2\/\u03b4 and PPAR\u03b3) are ligand-activated nuclear receptors, involved in the regulation of various metabolic and cellular processes, thus serving as potential drug targets for a variety of pathologies. Yet, given that PPARs\u2019 agonists can have pan-, dual- or isoform-specific action, some controversy has been raised over currently approved drugs and their side effects, highlighting the need for novel molecules. Here, we expand and validate a cell-based PPAR transactivation activity biosensor, and test it in a screening campaign to guide drug discovery. Biosensor upgrades included the use of different reporter genes to increase signal intensity and stability, a different promoter to modulate reporter gene expression, and multiplexing to improve efficiency. Sensor\u2019s limit of detection (LOD) ranged from 0.36\u20130.89 nM in uniplex and 0.89\u20131.35 nM in multiplex mode. In triplex mode, the sensor\u2019s feature screening, a total of 848 fractions of 96 cyanobacteria extracts were screened. Hits were confirmed in multiplex mode and in uniplex mode, yielding one strain detected to have action on PPAR\u03b1 and three strains to have dual action on PPAR\u03b1 and -\u03b2.<\/jats:p>","DOI":"10.3390\/s23031338","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:54:41Z","timestamp":1674622481000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Multiplex Molecular Cell-Based Sensor to Detect Ligands of PPARs: An Optimized Tool for Drug Discovery in Cyanobacteria"],"prefix":"10.3390","volume":"23","author":[{"given":"In\u00eas","family":"P\u00e1scoa","sequence":"first","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5410-4831","authenticated-orcid":false,"given":"Rita","family":"Biltes","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS-Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"FCUP-Faculty of Sciences, Department of Biology, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Jo\u00e3o","family":"Sousa","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS-Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal"},{"name":"FCUP-Faculty of Sciences, Department of Biology, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-5579","authenticated-orcid":false,"given":"Marco Aur\u00e9lio Correia","family":"Preto","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"FCUP-Faculty of Sciences, Department of Biology, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7697-386X","authenticated-orcid":false,"given":"Lu\u00eds Filipe","family":"Castro","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"FCUP-Faculty of Sciences, Department of Biology, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2412-8730","authenticated-orcid":false,"given":"Raquel","family":"Ruivo","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-9840","authenticated-orcid":false,"given":"Isabel","family":"Cunha","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0092-8674(00)80726-6","article-title":"A Unified Nomenclature System for the Nuclear Receptor Superfamily","volume":"97","author":"Auwerx","year":"1999","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/2231-4040.90879","article-title":"The Peroxisome Proliferator-Activated Receptor: A Family of Nuclear Receptors Role in Various Diseases","volume":"2","author":"Tyagi","year":"2011","journal-title":"J. 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