Metabolomic and genomic investigation of two North-Norwegian cyanobacterial isolates for bioprospecting of new compounds

Abstract

Cyanobacteria are an excellent source of bioactive natural products that can be used in the development of new medicinal drugs. The cyanobacterial genus Nostoc have proven to be prolific producers of molecules with exciting bioactivities, including anti-bacterial, anti-fungal, and anti-cancerous. This feature combined with the Nostoc’s complex life cycle and sizeable genomes make them interesting targets for bioprospecting. During this thesis, a typical natural product discovery pipeline was carried out to investigate some of the genomic and metabolomic characteristics of two Nostoc sp. strains. The pipeline included prediction of the biosynthetic potential, liquid extraction of metabolites using a variation of solvents, reverse-phase fractionation, bioassay to test for bioactivity, and the use of reverse-phase UHPLC-MS² and an informatic tool for dereplication and molecular networking. Some clear differences between the strains were observed in the prediction of metabolite production and in the extracted metabolites. Anti-bacterial activity was observed in extract fractions of both strains, and the dereplication process resulted in the discovery of a congener of the earlier described compound hapalosin which has been shown to reverse multi-drug resistance in cancer cells.