Omics based approaches for the identification of novel bioactive secondary metabolites from marine sponge derived bacterial isolates
University College Cork
Antibiotic resistance is a major threat to public health worldwide which, urgently requires the discovery and development of novel antimicrobial drugs with new modes of action. The principal goal of this project is the discovery of new bioactive secondary metabolites that may lead to the discovery of new antibiotics to help fight against the antibiotic resistance crisis. The marine environment is a unique habitat where deep-sea microorganisms, because of their ability to adapt to this extreme environment, have the potential to produce novel secondary metabolites with potent biological activities. Furthermore, microbes associated with marine sponges are exposed to highly competitive environments both physiologically and nutritionally which is likely to promote the production of novel secondary metabolites. The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity and marine Streptomyces strains host abundant small molecule biosynthetic gene clusters (smBGCs) which encode polyketides, Non ribosomal peptide synthases (NRPS), siderophore, bacteriocin and lantipeptides. In this respect, by focusing on Streptomyces samples taken from sponges in marine environments off the Irish coast, we aimed to characterize new marine derived bacterial strains and to explore their bioactive potential. In order to maximize the number of potential novel bioactive metabolites that could be be identified from each Streptomyces strain, and to generate the most detailed information underpinning their associated metabolic pathways, the One Strain MAny Compounds (OSMAC) approach, combined with a multi-omics approach, was employed in this project. In total, the Streptomyces isolates (B226SN104, SM3 and SM9), produced 612 metabolites including but not limited to, Bisucaberin B, Maculosin, Desferrioxamine B, Desferrioxamine E, Concanamycin B, Lipoamicoumacin B, Probestin, Surugamide A, Fiscalin B, Gibbestatin B and Antimycin A1. The Streptomyces isolates produced metabolites active against the growth 21 of antimicrobial-resistant microorganisms categorized as an “Urgent” or “Serious” threat by the World Health Organization (WHO), including Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus and Candida spp. In addition, other activities of biomedical interest were identified, namely anti-cancer, anti-inflammatory and antioxidant activities. Furthermore, the omics approach allowed us to predict 19 potential bioactive and potential novel promising molecules from the Streptomyces SM9 isolate. Taken together, this project demonstrated the significant potential the modified OSMAC/multi omics approach could have in expanding the number of novel secondary and bioactive metabolites that could be generated from existing environmental microbial isolates. Furthermore, it has contributed to the fight against antimicrobial resistance by identifying as of yet potential undiscovered molecules with antimicrobial potential.
OSMAC , Omics , Bioinformatics , LC-MS/MS , Marine Streptomyces , Secondary metabolites , Natural product discovery , Molecular network , Bioactive metabolites , Antimicrobial resistance crisis , Metabolomics , Microbiology , Genomics , Bioactive molecular network , Crude extracts , Biosynthetic gene clusters sm(BGC) , Bioactivity screening
Patry, S. A. D. 2021. Omics based approaches for the identification of novel bioactive secondary metabolites from marine sponge derived bacterial isolates. PhD Thesis, University College Cork.