Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source

Previous studies revealed the potential of <i>Labrenzia aggregata</i> USBA 371 to produce cytotoxic metabolites. This study explores its metabolic diversity and compounds involved in its cytotoxic activity. Extracts from the extracellular fraction of strain USBA 371 showed high levels of...

Full description

Bibliographic Details
Main Authors: Carolina Díaz-Cárdenas, Laura Yinneth Rojas, Susana Fiorentino, Monica P. Cala, Jorge I Díaz, Freddy A. Ramos, Jean Armengaud, Silvia Restrepo, Sandra Baena
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/11/2546
_version_ 1797566637095780352
author Carolina Díaz-Cárdenas
Laura Yinneth Rojas
Susana Fiorentino
Monica P. Cala
Jorge I Díaz
Freddy A. Ramos
Jean Armengaud
Silvia Restrepo
Sandra Baena
author_facet Carolina Díaz-Cárdenas
Laura Yinneth Rojas
Susana Fiorentino
Monica P. Cala
Jorge I Díaz
Freddy A. Ramos
Jean Armengaud
Silvia Restrepo
Sandra Baena
author_sort Carolina Díaz-Cárdenas
collection DOAJ
description Previous studies revealed the potential of <i>Labrenzia aggregata</i> USBA 371 to produce cytotoxic metabolites. This study explores its metabolic diversity and compounds involved in its cytotoxic activity. Extracts from the extracellular fraction of strain USBA 371 showed high levels of cytotoxic activity associated with the production of diketopiperazines (DKPs). We purified two compounds and a mixture of two other compounds from this fraction. Their structures were characterized by 1D and 2D nuclear magnetic resonance (NMR). The purified compounds were evaluated for additional cytotoxic activities. Compound <b>1</b> (cyclo (<span style="font-variant: small-caps;">l</span>-Pro-<span style="font-variant: small-caps;">l</span>-Tyr)) showed cytotoxicity to the following cancer cell lines: breast cancer 4T1 (IC<sub>50</sub> 57.09 ± 2.11 µM), 4T1H17 (IC<sub>50</sub> 40.38 ± 1.94), MCF-7 (IC<sub>50</sub> 87.74 ± 2.32 µM), murine melanoma B16 (IC<sub>50</sub> 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (−) (IC<sub>50</sub> 291.32 ± 5.64) and MES-SA/Dx5 P-pg (+) (IC<sub>50</sub> 225.28 ± 1.23), and murine colon MCA 38 (IC<sub>50</sub> 29.85 ± 1.55). In order to elucidate the biosynthetic route of the production of DKPs and other secondary metabolites, we sequenced the genome of <i>L. aggregata</i> USBA 371. We found no evidence for biosynthetic pathways associated with cyclodipeptide synthases (CDPSs) or non-ribosomal peptides (NRPS), but based on proteogenomic analysis we suggest that they are produced by proteolytic enzymes. This is the first report in which the cytotoxic effect of cyclo (<span style="font-variant: small-caps;">l</span>-Pro-<span style="font-variant: small-caps;">l</span>-Tyr) produced by an organism of the genus <i>Labrenzia</i> has been evaluated against several cancer cell lines.
first_indexed 2024-03-10T19:29:16Z
format Article
id doaj.art-00e309f5ff2546cea02221d0bef143a8
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-10T19:29:16Z
publishDate 2020-05-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-00e309f5ff2546cea02221d0bef143a82023-11-20T02:14:08ZengMDPI AGMolecules1420-30492020-05-012511254610.3390/molecules25112546Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial SourceCarolina Díaz-Cárdenas0Laura Yinneth Rojas1Susana Fiorentino2Monica P. Cala3Jorge I Díaz4Freddy A. Ramos5Jean Armengaud6Silvia Restrepo7Sandra Baena8Unidad de Saneamiento y Biotecnología Ambiental, Departamento de Biología, Pontificia Universidad Javeriana, P.O. Box 56710 Bogotá DC, ColombiaGrupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, P.O. Box 56710 Bogotá DC, ColombiaGrupo de Inmunobiología y Biología Celular, Pontificia Universidad Javeriana, P.O. Box 56710 Bogotá DC, ColombiaMetabolomics Core Facility—MetCore, Vicepresidency for Research and Creation, Universidad de los Andes, Cra 1 No. 18A-12, 111711 Bogotá DC, ColombiaVicepresidency of Research and Creation, Universidad de los Andes, Cra 1 No. 18A-12, 111711 Bogotá DC, ColombiaDepartamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia-Sede Bogotá, Carrera 30 # 45-03, 110111 Bogotá DC, ColombiaDépartement Médicaments et Technologies pour la Santé (DMTS), CEA, INRAE, Université Paris Saclay, SPI, 30200 Bagnols-sur-Cèze, FranceChemical Engineering Department, Universidad de los Andes, Cra 1 No. 18A-12, 111711 Bogotá DC, ColombiaUnidad de Saneamiento y Biotecnología Ambiental, Departamento de Biología, Pontificia Universidad Javeriana, P.O. Box 56710 Bogotá DC, ColombiaPrevious studies revealed the potential of <i>Labrenzia aggregata</i> USBA 371 to produce cytotoxic metabolites. This study explores its metabolic diversity and compounds involved in its cytotoxic activity. Extracts from the extracellular fraction of strain USBA 371 showed high levels of cytotoxic activity associated with the production of diketopiperazines (DKPs). We purified two compounds and a mixture of two other compounds from this fraction. Their structures were characterized by 1D and 2D nuclear magnetic resonance (NMR). The purified compounds were evaluated for additional cytotoxic activities. Compound <b>1</b> (cyclo (<span style="font-variant: small-caps;">l</span>-Pro-<span style="font-variant: small-caps;">l</span>-Tyr)) showed cytotoxicity to the following cancer cell lines: breast cancer 4T1 (IC<sub>50</sub> 57.09 ± 2.11 µM), 4T1H17 (IC<sub>50</sub> 40.38 ± 1.94), MCF-7 (IC<sub>50</sub> 87.74 ± 2.32 µM), murine melanoma B16 (IC<sub>50</sub> 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (−) (IC<sub>50</sub> 291.32 ± 5.64) and MES-SA/Dx5 P-pg (+) (IC<sub>50</sub> 225.28 ± 1.23), and murine colon MCA 38 (IC<sub>50</sub> 29.85 ± 1.55). In order to elucidate the biosynthetic route of the production of DKPs and other secondary metabolites, we sequenced the genome of <i>L. aggregata</i> USBA 371. We found no evidence for biosynthetic pathways associated with cyclodipeptide synthases (CDPSs) or non-ribosomal peptides (NRPS), but based on proteogenomic analysis we suggest that they are produced by proteolytic enzymes. This is the first report in which the cytotoxic effect of cyclo (<span style="font-variant: small-caps;">l</span>-Pro-<span style="font-variant: small-caps;">l</span>-Tyr) produced by an organism of the genus <i>Labrenzia</i> has been evaluated against several cancer cell lines.https://www.mdpi.com/1420-3049/25/11/2546<i>Labrenzia aggregata</i> USBA 371cytotoxic activitiesbioactive natural productssaline natural productssecondary metabolismgenome annotation
spellingShingle Carolina Díaz-Cárdenas
Laura Yinneth Rojas
Susana Fiorentino
Monica P. Cala
Jorge I Díaz
Freddy A. Ramos
Jean Armengaud
Silvia Restrepo
Sandra Baena
Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
Molecules
<i>Labrenzia aggregata</i> USBA 371
cytotoxic activities
bioactive natural products
saline natural products
secondary metabolism
genome annotation
title Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
title_full Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
title_fullStr Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
title_full_unstemmed Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
title_short Bioactive Potential of Extracts of <i>Labrenzia aggregata</i> Strain USBA 371, a Halophilic Bacterium Isolated from a Terrestrial Source
title_sort bioactive potential of extracts of i labrenzia aggregata i strain usba 371 a halophilic bacterium isolated from a terrestrial source
topic <i>Labrenzia aggregata</i> USBA 371
cytotoxic activities
bioactive natural products
saline natural products
secondary metabolism
genome annotation
url https://www.mdpi.com/1420-3049/25/11/2546
work_keys_str_mv AT carolinadiazcardenas bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT laurayinnethrojas bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT susanafiorentino bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT monicapcala bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT jorgeidiaz bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT freddyaramos bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT jeanarmengaud bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT silviarestrepo bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource
AT sandrabaena bioactivepotentialofextractsofilabrenziaaggregataistrainusba371ahalophilicbacteriumisolatedfromaterrestrialsource