{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:04:54Z","timestamp":1761293094742,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2013,12,9]],"date-time":"2013-12-09T00:00:00Z","timestamp":1386547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Cyanobactins are a recently recognized group of ribosomal cyclic peptides produced by cyanobacteria, which have been studied because of their interesting biological activities. Here, we have used a PCR-based approach to detect the N-terminal protease (A) gene from cyanobactin synthetase gene clusters, in a set of diverse cyanobacteria from our culture collection (Laboratory of Ecotoxicology, Genomics and Evolution (LEGE) CC). Homologues of this gene were found in Microcystis and Rivularia strains, and for the first time in Cuspidothrix, Phormidium and Sphaerospermopsis strains. Phylogenetic relationships inferred from available A-gene sequences, including those obtained in this work, revealed two new groups of phylotypes, harboring Phormidium, Sphaerospermopsis and Rivularia LEGE isolates. Thus, this study shows that, using underexplored cyanobacterial strains, it is still possible to expand the known genetic diversity of genes involved in cyanobactin biosynthesis.<\/jats:p>","DOI":"10.3390\/md11124902","type":"journal-article","created":{"date-parts":[[2013,12,9]],"date-time":"2013-12-09T12:47:59Z","timestamp":1386593279000},"page":"4902-4916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["N-Terminal Protease Gene Phylogeny Reveals the Potential for Novel Cyanobactin Diversity in Cyanobacteria"],"prefix":"10.3390","volume":"11","author":[{"given":"Joana","family":"Martins","sequence":"first","affiliation":[{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto 4169-007, Portugal"},{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research,  University of Porto, Rua dos Bragas 289, Porto 4050-123, Portugal"}]},{"given":"Pedro","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research,  University of Porto, Rua dos Bragas 289, Porto 4050-123, Portugal"}]},{"given":"Vitor","family":"Ramos","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto 4169-007, Portugal"},{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research,  University of Porto, Rua dos Bragas 289, Porto 4050-123, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-2417","authenticated-orcid":false,"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto 4169-007, Portugal"},{"name":"CIIMAR\/CIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research,  University of Porto, Rua dos Bragas 289, Porto 4050-123, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2013,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1073\/pnas.1217107110","article-title":"Improving the coverage of the cyanobacterial phylum using diversity-driven genome sequencing","volume":"110","author":"Shih","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","first-page":"141","article-title":"The Natural Products Chemistry of Cyanobacteria","volume":"Volume 2","author":"Mander","year":"2010","journal-title":"Comprehensive Natural Products II Chemistry and Biology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nchembio.84","article-title":"A global assembly line for cyanobactins","volume":"4","author":"Donia","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_4","first-page":"539","article-title":"Cyanobactins\u2014Ubiquitous Cyanobacterial Ribosomal Peptide Metabolites","volume":"Volume 2","author":"Mander","year":"2010","journal-title":"Comprehensive Natural Products II. Chemistry and Biology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0076-6879(09)04823-X","article-title":"Chapter 23. Cyanobactin ribosomally synthesized peptides\u2014A case of deep metagenome mining","volume":"458","author":"Schmidt","year":"2009","journal-title":"Meth. Enzymol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.chembiol.2011.01.019","article-title":"Linking chemistry and genetics in the growing cyanobactin natural products family","volume":"18","author":"Donia","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1107\/S010827019300811X","article-title":"Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella","volume":"50","author":"In","year":"1994","journal-title":"Acta Crystallogr. C"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1021\/np0605790","article-title":"Venturamides A and B: Antimalarial constituents of the panamanian marine cyanobacterium Oscillatoria sp.","volume":"70","author":"Linington","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1021\/np800409z","article-title":"Isolation of aerucyclamides C and D and structure revision of microcyclamide 7806A: Heterocyclic ribosomal peptides from Microcystis aeruginosa PCC 7806 and their antiparasite evaluation","volume":"71","author":"Portmann","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1021\/np960178s","article-title":"Dendroamides, new cyclic hexapeptides from a blue-green alga. Multidrug-resistance reversing activity of dendroamide A","volume":"59","author":"Ogino","year":"1996","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7568","DOI":"10.1021\/jo015703t","article-title":"Solid-phase total synthesis of trunkamide A (1)","volume":"66","author":"Caba","year":"2001","journal-title":"J. Org. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1128\/AEM.02134-08","article-title":"Widespread occurrence and lateral transfer of the cyanobactin biosynthesis gene cluster in cyanobacteria","volume":"75","author":"Leikoski","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1007\/s00253-010-2482-x","article-title":"Cyanobactins\u2014Ribosomal cyclic peptides produced by cyanobacteria","volume":"86","author":"Sivonen","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e43002","DOI":"10.1371\/journal.pone.0043002","article-title":"Analysis of an inactive cyanobactin biosynthetic gene cluster leads to discovery of new natural products from strains of the genus Microcystis","volume":"7","author":"Leikoski","year":"2012","journal-title":"PLoS One"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/cbic.201290074","article-title":"The discovery of new cyanobactins from Cyanothece PCC 7425 defines a new signature for processing of patellamides","volume":"13","author":"Houssen","year":"2012","journal-title":"ChemBioChem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/np980396g","article-title":"Prenylagaramides A and B, new cyclic peptides from two strains of Oscillatoria agardhii","volume":"62","author":"Murakami","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"McIntosh, J.A., Lin, Z., Tianero, M.D., and Schmidt, E.W. (2013). Aesturamides, a natural library of cyanobactin cyclic peptides resulting from isoprene-derived Claisen rearrangements. ACS Chem. Biol.","DOI":"10.1021\/cb300614c"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1073\/pnas.0501424102","article-title":"Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patella","volume":"102","author":"Schmidt","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nchembio829","article-title":"Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians","volume":"2","author":"Donia","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1039\/C2NP20085F","article-title":"Ribosomally synthesized and post-translationally modified peptide natural products: Overview and recommendations for a universal nomenclature","volume":"30","author":"Arnison","year":"2012","journal-title":"Nat. Prod. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1099\/ijs.0.63276-0","article-title":"Phylogenetic and morphological evaluation of the genera Anabaena, Aphanizomenon, Trichormus and Nostoc (Nostocales, Cyanobacteria)","volume":"55","author":"Rajaniemi","year":"2005","journal-title":"Int. J. Syst. Ecol. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1128\/AEM.01061-09","article-title":"Highly diverse cyanobactins in strains of the genus Anabaena","volume":"76","author":"Leikoski","year":"2010","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5507\/fot.2009.005","article-title":"Nomenclatural validation of the genetically revised cyanobacterial genus Dolichospermum (Ralfs ex Bornet et Flahault) comb. nova","volume":"9","author":"Wacklin","year":"2009","journal-title":"Fottea"},{"key":"ref_24","first-page":"371","article-title":"Taxonomic consequences from the combined molecular and phenotype evaluation of selected Anabaena and Aphanizomenon strains","volume":"117","author":"Rajaniemi","year":"2005","journal-title":"Arch. Hydrobiol. Algol. Stud."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/j.1529-8817.2009.00758.x","article-title":"Polyphasic characterization of three strains of Anabaena reniformis and Aphanizomenon aphanizomenoides (cyanobacteria) and their reclassification to Sphaerospermum gen. nov. (incl. Anabaena kisseleviana)","volume":"45","author":"Hrouzek","year":"2009","journal-title":"J. Phycol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1099\/ijs.0.02744-0","article-title":"Polyphyly of true branching cyanobacteria (Stigonematales)","volume":"54","author":"Gugger","year":"2004","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1574-6968.2001.tb10736.x","article-title":"Evidence for polyphyletic origin of the members of the orders of Oscillatoriales and Pleurocapsales as determined by 16S rDNA analysis","volume":"201","author":"Ishida","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1023\/A:1015262621848","article-title":"A molecular test of cyanobacterial phylogeny: Inferences from constraint analyses","volume":"468","author":"Litvaitis","year":"2002","journal-title":"Hydrobiologia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1007\/PL00006517","article-title":"Detection of seven major evolutionary lineages in cyanobacteria based on the 16S rRNA gene sequence analysis with new sequences of five marine Synechococcus strains","volume":"48","author":"Honda","year":"1999","journal-title":"J. Mol. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00203-006-0204-7","article-title":"Genotypic and phenotypic diversity of cyanobacteria assigned to the genus Phormidium (Oscillatoriales) from different habitats and geographical sites","volume":"187","author":"Marquardt","year":"2007","journal-title":"Arch. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1099\/ijs.0.02821-0","article-title":"Molecular phylogeny of the heterocystous cyanobacteria (subsections IV and V) based on nifD","volume":"54","author":"Henson","year":"2004","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1099\/00207713-51-3-873","article-title":"A proposal for the unification of five species of the cyanobacterial genus Microcystis K\u00fctzing ex Lemmermann 1907 under the rules of the Bacteriological Code","volume":"51","author":"Otsuka","year":"2001","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_33","first-page":"2","article-title":"Patterns of growth and development in pleurocapsalean cyanobacteria","volume":"42","author":"Waterbury","year":"1978","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_34","first-page":"247","article-title":"Modern approach to the classification system of Cyanophytes: 4-Nostocales","volume":"82","author":"Anagnostidis","year":"1989","journal-title":"Arch. Hydrobiol. Suppl."},{"key":"ref_35","first-page":"548","article-title":"Cyanoprokaryota, Part 1: Chroococcales","volume":"Volume 19\/1","author":"Ettl","year":"1998","journal-title":"S\u00fcsswasserflora von Mitteleuropa"},{"key":"ref_36","first-page":"759","article-title":"Cyanoprokaryota, Part 2: Oscillatoriales","volume":"Volume 19\/2","author":"Krienitz","year":"2005","journal-title":"S\u00fcsswasserflora von Mitteleuropa"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10750-009-9977-4","article-title":"The Estela Sousa e Silva Algal Culture Collection: A resource of biological and toxicological interest","volume":"636","author":"Paulino","year":"2009","journal-title":"Hydrobiologia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","article-title":"CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice","volume":"22","author":"Thompson","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1093\/molbev\/msr121","article-title":"MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods","volume":"28","author":"Tamura","year":"2011","journal-title":"Mol. Biol. Evol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1099\/00207713-47-3-693","article-title":"rRNA sequences and evolutionary relationships among toxic and non-toxic cyanobacteria of the genus Microcystis","volume":"47","author":"Neilan","year":"1997","journal-title":"Int. J. Syst. Bacteriol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1128\/aem.63.8.3327-3332.1997","article-title":"PCR primers to amplify 16S rRNA genes from cyanobacteria","volume":"63","author":"Muyzer","year":"1997","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Blin, K., Medema, M.H., Kazempour, D., Fischbach, M.A., Breitling, R., Takano, E., and Weber, T. (2013). antiSMASH 2.0\u2014A versatile platform for genome mining of secondary metabolite producers. Nucleic Acids Res.","DOI":"10.1093\/nar\/gkt449"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01734359","article-title":"Evolutionary trees from DNA sequences: A maximum likelihood approach","volume":"17","author":"Felsenstein","year":"1981","journal-title":"J. Mol. Evol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/12\/4902\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:51:13Z","timestamp":1760219473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/12\/4902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,9]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12]]}},"alternative-id":["md11124902"],"URL":"https:\/\/doi.org\/10.3390\/md11124902","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2013,12,9]]}}}