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

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 (IC(50) 57.09 ± 2.11 µM), 4T1H17 (IC(50) 40.38 ± 1.94), MCF-7 (IC(50) 87.74 ± 2.32 µM), murine melanoma B16 (IC(50) 80.87 ± 3.67), human uterus sarcoma MES-SA/Dx5 P-pg (−) (IC(50) 291.32 ± 5.64) and MES-SA/Dx5 P-pg (+) (IC(50) 225.28 ± 1.23), and murine colon MCA 38 (IC(50) 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.