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In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(\/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D\/2D NMR spectroscopy, and Marfey\u2019s analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.<\/jats:p>","DOI":"10.3390\/md22060268","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T11:58:58Z","timestamp":1718107138000},"page":"268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cellulamides: A New Family of Marine-Sourced Linear Peptides from the Underexplored Cellulosimicrobium Genus"],"prefix":"10.3390","volume":"22","author":[{"given":"Mariana","family":"Gir\u00e3o","sequence":"first","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Jos\u00e9","family":"Murillo-Alba","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Parque Tecnol\u00f3gico de Ciencias de la Salud, 18016 Armilla, Spain"}]},{"given":"Jes\u00fas","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Parque Tecnol\u00f3gico de Ciencias de la Salud, 18016 Armilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-688X","authenticated-orcid":false,"given":"Ignacio","family":"P\u00e9rez-Victoria","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Parque Tecnol\u00f3gico de Ciencias de la Salud, 18016 Armilla, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-3895","authenticated-orcid":false,"given":"Ricardo B.","family":"Leite","sequence":"additional","affiliation":[{"name":"Genomics Unit, Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-9195","authenticated-orcid":false,"given":"Ralph","family":"Urbatzka","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-9164","authenticated-orcid":false,"given":"Pedro N.","family":"Le\u00e3o","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-0540","authenticated-orcid":false,"given":"Maria F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leix\u00f5es, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-5106","authenticated-orcid":false,"given":"Fernando","family":"Reyes","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n MEDINA, Centro de Excelencia en Investigaci\u00f3n de Medicamentos Innovadores en Andaluc\u00eda, Parque Tecnol\u00f3gico de Ciencias de la Salud, 18016 Armilla, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Oren, A., and Garrity, G.M. 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