Bioprospecting of Arctic marine organisms Employing bioassay-, chemistry-, and metabolomics-guided isolation

• Main Author: Olsen, Elisabeth Klungerbo
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: UiT The Arctic University of Norway 2015
• Subjects: VDP::Teknologi: 500::Bioteknologi: 590; VDP::Technology: 500::Biotechnology: 590; DOKTOR-002; Arctic
• Online Access: https://hdl.handle.net/10037/8145

The marine environment inhabits a large diversity of organisms that produce natural products as a strategy for survival. Many marine natural products are found to display different bioactivities and some of them have reached the market as drugs or dietary supplements. Comprehending the great potential of bioactive marine natural products motivates for the continuing bioprospecting of organisms from the oceans. In this thesis the aim was to isolate bioactive marine natural products. Three different approaches were studied, namely bioassay-, chemistry- and metabolomics-guided isolation. The bioassay-guided isolation approach yielded an antioxidative bromophenol isolated from the alga Vertebrata lanosa, which was active in both biochemical and cellular assays. It was more potent than the known antioxidants luteolin and quercetin in both cellular assays and of quercetin in one of the assays. Barettin was attributed an additional bioactivity as it, together with the structurally similar 8,9-dihydrobarettin, inhibited electric eel acetylcholine esterase (AChE). Inhibition by both barettins was in the range of the reported AChE inhibitors pulmonarin A and B and of the drug galanthamine. Two brominated indoles were isolated, using chemistry-guided isolation, from Geodia barretti based on their structural similarities with barettin and 8,9-dihydrobarettin. The brominated indoles were used as inspiration for synthesising a library of 22 structurally similar compounds. Synthetic compounds having a combination of a bromine substituent in a specific structural position and a positively charged amine were the most potent. However, the brominated indole was found not to be sufficient for AChE inhibition. Metabolomics-guided isolation was used to study the differences in natural products produced by the closely related sponges G. barretti and G. macandrewii. Employing this bioprospecting approach a novel compound unique for G. macandrewii was identified and it was suggested that metabolomics could be a valuable supplement to other bioprospecting approaches like the bioassay-guided isolation.