Show simple item record

dc.contributor.advisorRämä, Teppo
dc.contributor.authorHagestad, Ole Christian
dc.date.accessioned2021-05-30T09:28:11Z
dc.date.available2021-05-30T09:28:11Z
dc.date.issued2021-06-17
dc.description.abstractMarine fungi comprise a group of organisms that have been overlooked for a long time. Research interest has increased with the realization of the important ecological role and rich chemistry of marine fungi. Marine fungi have yielded thousands of new natural products the last decade, but many taxa remain unstudied. Marine fungi from the Arctic have not been reported in literature in regard to bioprospecting campaigns and represent a novel source of natural products. The aim of this thesis is to assess the potential of Arctic marine fungi to produce bioactive secondary metabolites by fermentation and genome analysis. This was achieved in three steps. First, fungi were isolated from the Svalbard archipelago. The 20 isolates obtained were characterized based on molecular markers and their antibacterial activity was tested using an agar diffusion assay (Paper 1). Secondly, three distinct marine fungi were whole genome sequenced and characterized. One of the fungi represented a putatively novel species which was circumscribed based on morphology and phylogenetic inference (Paper 2). Finally, a metabolite from one fungus among the 20 obtained around Svalbard was isolated and the bioactivities characterized (Paper 3). In Paper 1, half of the fungal isolates showed activity against pathogenic bacteria and every third isolate represents potentially new species of fungi. Five of these isolates are strictly marine fungi belonging to the order of Lulworthiales. The study showed that the Arctic can yield novel marine fungal diversity that can be utilized in bioprospecting. For Paper 2, three marine fungi were whole genome sequenced and their biosynthetic gene clusters were characterized. Mapping of the biosynthetic gene clusters (BGCs) within the Emericellopsis genome confirmed the detection of the secondary metabolite helvolic acid produced during fermentation. The study revealed numerous unknown biosynthetic gene clusters and a range of carbohydrate active enzymes. Each of the three genomes provides the first genome of their respective taxa and can contribute to understanding their evolutionary adaption to the marine environment. In Paper 3, a novel compound from the fermentation broth of Mytilinidion sp. was isolated and its bioactivity was characterized using seven different bioactivity assays. The compound turned out to be a modified medium component with IC50 of 43 µM in an ACE-inhibitory assay. The compound was novel and this is the first report of its bioactivity. Molecular networking could perhaps have provided early indications that the compound was a modified medium component.en_US
dc.description.abstractMarin sopp er en gruppe av organismer som har vært oversett i lang tid. Interessen for marin sopp har steget i takt med økt forståelse for dens økologi og rike kjemi. Mange tusen nye naturprodukter har blitt beskrevet fra marin sopp de siste tiårene, men det er fremdeles mange grupper som ikke er godt studert. Marin sopp fra Arktis er ikke godt undersøkt i forbindelse med bioprospektering og representerer en ny kilde til naturprodukter. Målet med avhandlingen var å vurdere potensialet til Arktisk marin sopp for å produsere bioaktive metabolitter ved å bruke fermentering og genomanalyse. Dette ble gjennomført i tre steg. Først ble 20 marine sopp isolert i løpet av ett forskningstokt rundt Svalbard. Disse soppene ble karakterisert ved hjelp av molekylære markører og evnen til å produsere antibakterielle forbindelser ble undersøkt ved å bruke agar-diffusjons analyse (Artikkel 1). Det neste som ble gjort var at tre forskjellige marine sopp ble helgenomsekvensert og genomene ble karakterisert. En av soppene er antageligvis ny for vitenskapen og ble beskrevet basert på morfologisk og fylogenetisk analyser (Artikkel 2). Til sist ble ett stoff fra en av soppene fra Artikkel 1 isolert og bioaktiviteten til stoffet ble beskrevet (Artikkel 3). I den første artikkelen viste halvparten av de isolerte soppene antibakteriell aktivitet mot sykdomsfremkallende bakterier. Hvert tredje isolat representerer muligens nye arter basert på tilgjengelige referansesekvenser. Fem av de potensielt nye artene tilhører ordenen Lulworthiales som kun finnes i havet. Studien har vist at det er stort potensiale for å avdekke nye arter og at mange av disse viser evne til å produsere antibakterielle forbindelser. Dette viser at de kan utnyttes i bioprospektering. I Artikkel 2 ble tre ulike marine sopper helgenomsekvenseert og genomet ble karakterisert med tanke på hvilke biosyntetiske genklynger og karbohydrat-aktive enzymer som ble detektert. Karakteriseringen av genklyngene i Emericellopsis bekreftet deteksjonen av metabolitten helvolsyre som soppen produserte under fermentering. Studien avslørte mange ukjente genklynger og en rekke karbohydrat-aktive enzymer. De tre genomene er de første helsekvenserte genomene i deres respektive slekter og kan bidra til å gi ny kunnskap om de evolusjonære tilpasningene de har til det marine miljø. I den siste artikkelen ble ett ukjent stoff fra fermenteringen av Mytilinidion isolert. Bioaktiviteten til stoffet ble karakterisert ved hjelp av syv forskjellige bioaktivitetstester. Stoffet viste seg å være en delvis nedbrutt og modifisert mediekomponent som hadde en IC50 verdi på 42.3 µM i en ACE-inhiberingstest. Analyse ved hjelp av molekylært nettverk kunne kanskje avdekket at stoffet var relatert til dyrkningsmediumet.en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractThe thesis introduces Arctic marine fungi and their potential for utilization in natural product discovery. Paper 1 deals with diversity and antibacterial activity of marine fungi isolated around Svalbard. The result shows that the Arctic hosts novel fungal diversity that have antibacterial activity, which can be utilized in biodiscovery. Paper 2 describes a new species and examines the genomes of three marine fungi for biosynthetic gene clusters. One of the fungi was fermented and tested for different bioactivities. The metabolite helvolic acid was detected in the fermentation broth and this was further confirmed by the presence of its biosynthetic gene cluster. In addition, we examined the carbohydrate-active enzymes of the three genomes that can potentially be used in industrial applications. In Paper 3, we show one of the challenges in isolation of metabolites by using a Mytilinidion sp. as a case study and propose a way to overcome the challenge in the future.en_US
dc.description.sponsorshipThe work presented in this thesis was carried out at the Norwegian College of Fishery Sciences (NFH), UiT – The Arctic University of Norway from January 2017 to April 2021. The work was funded by UiT - The Arctic University of Norway as an independent PhD position.en_US
dc.identifier.isbn978-82-8266-200-0
dc.identifier.urihttps://hdl.handle.net/10037/21270
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper 1: Hagestad, O.C., Andersen, J.H., Altermark, B., Hansen, E. & Rämä, T. (2020). Cultivable marine fungi from the Arctic Archipelago of Svalbard and their antibacterial activity. <i>Mycology, 11</i>(3), 230-242. Also available in Munin at <a href=https://hdl.handle.net/10037/17692>https://hdl.handle.net/10037/17692</a>. <p>Paper 2: Hagestad, O.C., Hou, L., Andersen, J.H., Hansen, E.H., Altermark, B., Li, C., … Rämä, T. Genomic characterization of three marine fungi, including <i>Emericellopsis atlantica</i> sp. nov. with signatures of a generalist lifestyle and marine biomass degradation. (Submitted manuscript). <p>Paper 3: Hagestad, O.C., Hanssen, K.Ø., Isaksson, J., Andersen, J.H., Hansen, E.H. & Rämä, T. Pitfalls in biodiscovery – a case study of <i>Mytilinidion</i> sp. M16HEL1360D1-10.1, a wood-associated fungus from the marine environment in the Arctic. (Manuscript).en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)en_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::General microbiology: 472en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Generell mikrobiologi: 472en_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Genetics and genomics: 474en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474en_US
dc.subjectVDP::Mathematics and natural science: 400::Zoology and botany: 480::Marine biology: 497en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480::Marinbiologi: 497en_US
dc.subjectVDP::Technology: 500::Biotechnology: 590en_US
dc.subjectVDP::Teknologi: 500::Bioteknologi: 590en_US
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Bioinformatics: 475en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Bioinformatikk: 475en_US
dc.titleBioprospecting of marine fungi from the High Arctic: A study of high latitude marine fungi from understudied taxa; bioactivity potential, taxonomy and genomicsen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


File(s) in this item

Thumbnail
Thumbnail

This item appears in the following collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)