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

Abstract

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.

Metagenomic analysis of the soil microbial composition and salt tolerance mechanism in Yuncheng Salt Lake, Shanxi Province

“…Using the purple membrane of extreme halophiles may also lead to the development of new technical products in the electronics field. Halophilic microorganisms also produce substances with special, bioactive properties ( Díaz-Cárdenas et al, 2020 ; Martínez-Pérez et al, 2020 ). Therefore, research on halophilic compounds has certain theoretical and practical value.…”

Recent Antimicrobial Responses of Halophilic Microbes in Clinical Pathogens

“…In the future, halogenated drugs may have increased action against drug-resistant bacteria [136,137]. OMIC technologies present new potential for the discovery of exclusive properties and/or novel biomolecules derived from halophiles in the future [138,139] as a result of recent findings of halophilic bacteria, even from terrestrial environments [140].…”

“…[136,137]. OMIC technologies present new potential for the discovery of exclusive properties and/or novel biomolecules derived from halophiles in the future [138,139]as a result of recent findings of halophilic bacteria, even from terrestrial environments [140]. Further research is needed to report on how halophilic microorganisms evolved during the early phases of evolution of life on earth, as well as how they diversified and spread around the world.…”