Abstract
Identification of novel bioactive compounds represents an important field in modern biomedical research. Microorganisms of the underexplored environments, such as deserts, hot springs, oceans, and caves are highly promising candidates for screening such metabolites. Screening for biosynthetic genes is the most effective strategy to characterize bioactivity in a certain environment. However, knowledge is either scant or non-existent about the expression of the biosynthetic genes encoding for various bioactive compounds in the microorganisms from the caves. The aim of the current study was to screen for the genes of polyketide synthases and non-ribosomal peptide synthetases in Krubera–Voronja Cave (43.4184 N 40.3083 E, Western Caucasus) bacterial isolates as well as to evaluate the expression of these genes under laboratory conditions. In total, 91 bacterial strains isolated from the cave were screened for the presence of polyketide synthase and non-ribosomal peptide synthetase genes. Phenotypically inactive strains were the main focus (the test group) of our study, while the strains with the identified antibacterial activity served as the control group. Our PCR-based screening clearly showed that the majority of the strains harbored at least one biosynthetic gene. Prediction of the putative products allowed us to identify bioactive compounds with antibacterial, anticancer, antifungal, anti-inflammatory, antimycoplasmic, antiviral, insecticidal, and thrombolytic activity. For most polyketide synthases and non-ribosomal peptide synthetases, putative products could not be predicted; they are unknown. Qualitative transcriptional analysis did not show substantial differences between the test group and the control group of the strains. One to four biosynthetic genes were constitutively expressed in all the tested strains, irrespective of the group. Quantitative transcriptional analysis of the constitutively expressed biosynthetic genes demonstrated that the expression of a particular gene could be affected by both the amount of the nutrients in the culture medium and the growth phase.
Highlights
Identification of novel compounds with antibacterial, antifungal, anticancer, antiviral, antidiabetic, antiprotozoal, and other bioactivities constitutes an important field of the modern biomedical research
The aim of the current study was to perform a screening for the biosynthetic genes encoding PKS and NRPS in the Krubera–Voronja Cave isolates, and to determine if these genes are expressed under laboratory conditions
91 bacterial strains isolated from Krubera–Voronja Cave were screened for the presence of PKS and NRPS genes
Summary
Identification of novel compounds with antibacterial, antifungal, anticancer, antiviral, antidiabetic, antiprotozoal, and other bioactivities constitutes an important field of the modern biomedical research. Microorganisms are the main targets in this research field because of the high potential to produce these bioactive compounds. Microorganisms from the underexplored environments, such as deserts, hot springs, oceans, and caves are highly promising candidates for the screening of novel bioactive metabolites (Ghosh et al, 2017). It should be noted that the bioactive potential of the cave microorganisms is still poorly characterized. Cultivation-based phenotypic analysis was carried out in order to evaluate the antifungal, anticancer, and most frequently, the antibacterial activity (Ghosh et al, 2017; Belyagoubi et al, 2018). The chemical structure of the bioactive compounds was determined (Herold et al, 2005; Stankovic et al, 2012; Jiang et al, 2015, 2018; Lamprinou et al, 2015; Axenov-Gribanov et al, 2016)
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