TY - JOUR
T1 - Bioactive potential of extracts of Labrenzia aggregate strain USBA 371, a halophilic bacterium isolated from a terrestrial source
AU - Díaz-Cárdenas, Carolina
AU - Rojas, Laura Yinneth
AU - Fiorentino, Susana
AU - Cala, Monica P.
AU - Díaz, Jorge I.
AU - Ramos, Freddy A.
AU - Armengaud, Jean
AU - Restrepo, Silvia
AU - Baena, Sandra
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6
Y1 - 2020/6
N2 - Previous studies revealed the potential of Labrenzia aggregata 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 1 (cyclo (l-Pro-l-Tyr)) showed cytotoxicity to the following cancer cell lines: breast cancer 4T1 (IC50 57.09 ± 2.11 μM), 4T1H17 (IC50 40.38 ± 1.94), MCF-7 (IC50 87.74 ± 2.32 μM), murine melanoma B16 (IC50 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (-) (IC50 291.32 × 5.64) and MES-SA/Dx5 P-pg (+) (IC50 225.28 ± 1.23), and murine colon MCA 38 (IC50 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 L. aggregata 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 (l-Pro-l-Tyr) produced by an organism of the genus Labrenzia has been evaluated against several cancer cell lines.
AB - Previous studies revealed the potential of Labrenzia aggregata 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 1 (cyclo (l-Pro-l-Tyr)) showed cytotoxicity to the following cancer cell lines: breast cancer 4T1 (IC50 57.09 ± 2.11 μM), 4T1H17 (IC50 40.38 ± 1.94), MCF-7 (IC50 87.74 ± 2.32 μM), murine melanoma B16 (IC50 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (-) (IC50 291.32 × 5.64) and MES-SA/Dx5 P-pg (+) (IC50 225.28 ± 1.23), and murine colon MCA 38 (IC50 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 L. aggregata 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 (l-Pro-l-Tyr) produced by an organism of the genus Labrenzia has been evaluated against several cancer cell lines.
KW - Bioactive natural products
KW - Cytotoxic activities
KW - Genome annotation
KW - Labrenzia aggregata USBA 371
KW - NMR characterization
KW - Saline natural products
KW - Secondary metabolism
UR - http://www.scopus.com/inward/record.url?scp=85085909259&partnerID=8YFLogxK
U2 - 10.3390/molecules25112546
DO - 10.3390/molecules25112546
M3 - Article
C2 - 32486092
AN - SCOPUS:85085909259
SN - 1420-3049
VL - 25
JO - Molecules
JF - Molecules
IS - 11
M1 - 2546
ER -
