Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites
Natural products have been used by humans since ancient times as benefactors for improved health. Prior to modern medicine and chemistry, these compounds remained hidden in the plants, animals and other organisms used to heal inflammation, wounds, headache and stomachache among other conditions. Sin...
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Format: | Doctoral or Postdoctoral Thesis |
Language: | English |
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UiT The Arctic University of Norway
2021
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Online Access: | https://hdl.handle.net/10037/23299 |
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ftunivtroemsoe:oai:munin.uit.no:10037/23299 |
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openpolar |
institution |
Open Polar |
collection |
University of Tromsø: Munin Open Research Archive |
op_collection_id |
ftunivtroemsoe |
language |
English |
topic |
VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472 VDP::Mathematics and natural science: 400::Basic biosciences: 470::General microbiology: 472 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476 VDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476 DOKTOR-002 |
spellingShingle |
VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472 VDP::Mathematics and natural science: 400::Basic biosciences: 470::General microbiology: 472 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476 VDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476 DOKTOR-002 Kristoffersen, Venke Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
topic_facet |
VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472 VDP::Mathematics and natural science: 400::Basic biosciences: 470::General microbiology: 472 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476 VDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476 DOKTOR-002 |
description |
Natural products have been used by humans since ancient times as benefactors for improved health. Prior to modern medicine and chemistry, these compounds remained hidden in the plants, animals and other organisms used to heal inflammation, wounds, headache and stomachache among other conditions. Since the start of modern drug discovery with isolation of morphine in 1805, numerous natural products have been isolated from plants, animals, macroorganisms and microorganisms. Today, natural products, or their derivatives, are used as pharmaceuticals within a wide range of therapeutic areas, including cancer, pathogenic infections, inflammation and pain. Microbial natural products have played a particularly important role in the field of antibiotics. The discovery of penicillin from the Pencillium rubens fungus by Alexander Fleming in 1928 marked the beginning of the “Golden Age” of antibiotics that lasted until 1962, where most antibiotic classes in clinical use today were discovered. Several marketed drugs originate from marine microorganisms. Marine microorganisms are underexplored, thus representing a potential source for discovering novel bioactive compounds. In this project, Arctic marine microorganisms were fermented under different conditions based on the OSMAC approach and evaluated for their production of antibacterial and cytotoxic compounds. In paper I, a Pseudomonas sp. bacterium was cultivated in different growth media. The fermentation extracts were fractionated and tested for bioactivity, revealing different bioactivity profiles of the fractions from the different media. Dereplication of the active fractions by UHPLC-HR-MS and molecular networking led to identification of six rhamnolipid compounds, including one novel mono-rhamnolipid. All six compounds had antimicrobial activities, while three had cytotoxic activities. In paper II, a fractionated extract of the bacterium Lacinutrix sp. displayed antibacterial activity. Dereplication of the active fraction resulted in identification of two lyso-ornithine lipids, 1 and 2 . The compounds were isolated and their structures were elucidated with UHPLC-HR-MS and NMR. Bioactivity screening showed that 1 had antibacterial activity, while 2 had cytotoxic activity. In paper III, the fungus Digitatispora marina was fermented under different cultivation conditions. Fermentation extracts were fractionated and bioactivity screening of the fractions revealed antibacterial and cytotoxic activities. UHPLC-HR-MS analysis of the fractions showed a compound with an isotope distribution pattern for an ion with a single chlorine atom. The compound was isolated, and structure elucidation with NMR identified it as chlovalicin B. Its bioactive properties were broadly evaluated, revealing it had weak cytotoxic activity but no antimicrobial activities. |
format |
Doctoral or Postdoctoral Thesis |
author |
Kristoffersen, Venke |
author_facet |
Kristoffersen, Venke |
author_sort |
Kristoffersen, Venke |
title |
Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
title_short |
Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
title_full |
Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
title_fullStr |
Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
title_full_unstemmed |
Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
title_sort |
bioprospecting of arctic marine microorganisms. exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites |
publisher |
UiT The Arctic University of Norway |
publishDate |
2021 |
url |
https://hdl.handle.net/10037/23299 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Arctic |
genre_facet |
Arctic Arctic |
op_relation |
Paper I: Kristoffersen, V., Rämä, T., Isaksson, J., Andersen, J.H., Gerwick, W.H. & Hansen, E. (2018). Characterization of Rhamnolipids Produced by an Arctic Marine Bacterium from the Pseudomonas fluorescence Group. Marine Drugs, 16 (5), 163. Also available in Munin at https://hdl.handle.net/10037/13600 . Paper II: Kristoffersen, V., Jenssen, M., Jawad, H.R., Isaksson, J., Hansen, E.H., Rämä, T., Hansen, K.Ø. & Andersen, J.H. (2021). Two Novel Lyso-Ornithine Lipids Isolated from an Arctic Marine Lacinutrix sp. Bacterium. Molecules, 26 (17), 5295. Also available in Munin at https://hdl.handle.net/10037/22581 . Paper III: Jenssen, M., Kristoffersen, V., Motiram-Corral, K., Isaksson, J., Rämä, T., Andersen, J.H., Hansen, E.H. & Hansen, K.Ø. Chlovalicin B, a Chlorinated Sesquiterpene Isolated from the Arctic Marine Mushroom Digitatispora marina . (Manuscript). Now published in Molecules, 2021, 26 (24), 7560, available at https://doi.org/10.3390/molecules26247560 . 978-82-8266-210-9 https://hdl.handle.net/10037/23299 |
op_rights |
openAccess Copyright 2021 The Author(s) |
_version_ |
1766297403310211072 |
spelling |
ftunivtroemsoe:oai:munin.uit.no:10037/23299 2023-05-15T14:24:58+02:00 Bioprospecting of Arctic marine microorganisms. Exploring microbial secondary metabolite production using the one strain-many compounds approach: isolation and characterization of secondary metabolites Kristoffersen, Venke 2021-12-20 https://hdl.handle.net/10037/23299 eng eng UiT The Arctic University of Norway UiT Norges arktiske universitet Paper I: Kristoffersen, V., Rämä, T., Isaksson, J., Andersen, J.H., Gerwick, W.H. & Hansen, E. (2018). Characterization of Rhamnolipids Produced by an Arctic Marine Bacterium from the Pseudomonas fluorescence Group. Marine Drugs, 16 (5), 163. Also available in Munin at https://hdl.handle.net/10037/13600 . Paper II: Kristoffersen, V., Jenssen, M., Jawad, H.R., Isaksson, J., Hansen, E.H., Rämä, T., Hansen, K.Ø. & Andersen, J.H. (2021). Two Novel Lyso-Ornithine Lipids Isolated from an Arctic Marine Lacinutrix sp. Bacterium. Molecules, 26 (17), 5295. Also available in Munin at https://hdl.handle.net/10037/22581 . Paper III: Jenssen, M., Kristoffersen, V., Motiram-Corral, K., Isaksson, J., Rämä, T., Andersen, J.H., Hansen, E.H. & Hansen, K.Ø. Chlovalicin B, a Chlorinated Sesquiterpene Isolated from the Arctic Marine Mushroom Digitatispora marina . (Manuscript). Now published in Molecules, 2021, 26 (24), 7560, available at https://doi.org/10.3390/molecules26247560 . 978-82-8266-210-9 https://hdl.handle.net/10037/23299 openAccess Copyright 2021 The Author(s) VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472 VDP::Mathematics and natural science: 400::Basic biosciences: 470::General microbiology: 472 VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497 VDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497 VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Biokjemi: 476 VDP::Mathematics and natural science: 400::Basic biosciences: 470::Biochemistry: 476 DOKTOR-002 Doctoral thesis Doktorgradsavhandling 2021 ftunivtroemsoe 2021-12-22T23:55:52Z Natural products have been used by humans since ancient times as benefactors for improved health. Prior to modern medicine and chemistry, these compounds remained hidden in the plants, animals and other organisms used to heal inflammation, wounds, headache and stomachache among other conditions. Since the start of modern drug discovery with isolation of morphine in 1805, numerous natural products have been isolated from plants, animals, macroorganisms and microorganisms. Today, natural products, or their derivatives, are used as pharmaceuticals within a wide range of therapeutic areas, including cancer, pathogenic infections, inflammation and pain. Microbial natural products have played a particularly important role in the field of antibiotics. The discovery of penicillin from the Pencillium rubens fungus by Alexander Fleming in 1928 marked the beginning of the “Golden Age” of antibiotics that lasted until 1962, where most antibiotic classes in clinical use today were discovered. Several marketed drugs originate from marine microorganisms. Marine microorganisms are underexplored, thus representing a potential source for discovering novel bioactive compounds. In this project, Arctic marine microorganisms were fermented under different conditions based on the OSMAC approach and evaluated for their production of antibacterial and cytotoxic compounds. In paper I, a Pseudomonas sp. bacterium was cultivated in different growth media. The fermentation extracts were fractionated and tested for bioactivity, revealing different bioactivity profiles of the fractions from the different media. Dereplication of the active fractions by UHPLC-HR-MS and molecular networking led to identification of six rhamnolipid compounds, including one novel mono-rhamnolipid. All six compounds had antimicrobial activities, while three had cytotoxic activities. In paper II, a fractionated extract of the bacterium Lacinutrix sp. displayed antibacterial activity. Dereplication of the active fraction resulted in identification of two lyso-ornithine lipids, 1 and 2 . The compounds were isolated and their structures were elucidated with UHPLC-HR-MS and NMR. Bioactivity screening showed that 1 had antibacterial activity, while 2 had cytotoxic activity. In paper III, the fungus Digitatispora marina was fermented under different cultivation conditions. Fermentation extracts were fractionated and bioactivity screening of the fractions revealed antibacterial and cytotoxic activities. UHPLC-HR-MS analysis of the fractions showed a compound with an isotope distribution pattern for an ion with a single chlorine atom. The compound was isolated, and structure elucidation with NMR identified it as chlovalicin B. Its bioactive properties were broadly evaluated, revealing it had weak cytotoxic activity but no antimicrobial activities. Doctoral or Postdoctoral Thesis Arctic Arctic University of Tromsø: Munin Open Research Archive Arctic |