Coupling butyryl-coenzyme A oxidation to oxygen reduction in Fusobacterium nucleatum
department or school: Science, Irving K. Barber Faculty of (Okanagan)
department or school: Chemistry, Department of (Okanagan)
data provider: DSpace
degree campus: UBCO
creator: Bystrom, Liam
issued: 2024-11-18T22:53:34Z
issued: 2024
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Fusobacterium nucleatum is a Gram-negative obligate anaerobe and a normal constituent of the human oral cavity. Additionally, F. nucleatum can disseminate through the bloodstream of its host and colonize distal sites including tumors of the colon where it can exacerbate disease. In the host, F. nucleatum encounters oxygen as well as derivative reactive oxygen and nitrogen species, but there is limited information on oxidative and nitrosative defense mechanisms present in F. nucleatum. Examination of F. nucleatum subsp. polymorphum’s genome revealed the presence of a putative flavodiiron protein (FDP) which is known to reduce O₂ and/or NO to H₂O or N₂O, respectively. Colocalized with the FDP gene is a gene encoding a multicomponent enzyme called butyryl-CoA reductase (BCR). BCR contains three distinct domains: butyryl-CoA dehydrogenase (BCD), the C-terminal domain of the α-subunit of an electron transfer flavoprotein (ETFα), and rubredoxin (Rd). This thesis details work which shows that BCR functions to oxidize butyryl-CoA and transfer the reducing equivalents to the FDP for reduction of O₂ to H₂O. Electron transfer is dependent on the formation of a neutral semiquinone of the FAD bound to BCD and an anionic semiquinone of the FAD bound to ETFα. This enzyme pair gives F. nucleatum the ability to use a common metabolite (butyryl-CoA) with a high reduction potential to reduce O₂ and prevent oxidative stress. By using butyryl-CoA as reductant, F. nucleatum can derive additional energy from its amino acid-based metabolism while simultaneously removing toxic O₂. The novel BCR-FDP is one of the only enzymes characterized from F. nucleatum to function in oxidative stress defense, making it a potentially critical enzyme for F. nucleatum’s survival and subsequent infection. Bioinformatic analysis revealed that BCR-FDP is prevalent in many species of anaerobic gut bacteria where it may function in maintaining anaerobiosis and therefore a healthy gut microbiome.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89672
note: i COUPLING BUTYRYL-COENZYME A OXIDATION TO OXYGEN REDUCTION IN FUSOBACTERIUM NUCLEATUM By Liam Bystrom B.Sc., The University of British Columbia (Okanagan), 2022 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR MASTER OF SCIENCE in THE COLLEGE OF GRADUATE STUDIES (Biochemistry and Molecular Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) November 2024 © Liam Bystrom, 2024 ii The following individuals certify that they have read, and recommend to the College of Graduate Studies for acceptance, a thesis entitled: COUPLING BUTYRYL-COENYZME A OXIDATION TO OXYGEN REDUCTION IN FUSOBACTERIUM NUCLEATUM Submitted by Liam Bystrom in partial fulfillment of the requirements of the degree of Master of Science Dr. Kirsten Wolthers, Irving K. Barber Faculty of Science, University of British Columbia, Okanagan Supervisor Dr. Stephen McNeil, Irving K. Barber Faculty of Science, University of British Columbia, Okanagan Supervisory Committee Member Dr. Richard Plunkett, Irving K. Barber Faculty of Science, University of British Columbia, Okanagan Supervisory Committee Member Dr. Michael Deyholos, Irving K. Barber Faculty of Science, University of British Columbia, Okanagan University Examiner iii Abstract Fusobacterium nucleatum is a Gram-negative obligate anaerobe and a normal constituent of the human oral cavity. Additionally, F. nucleatum can disseminate through the bloodstream of its host and colonize distal sites including tumors of the colon where it can exacerbate disease. In the host, F. nucleatum encounters oxygen as well as derivative reactive oxygen and nitrogen species, but there is limited information on oxidative and nitrosative defense mechanisms present in F. nucleatum. Examination of F. nucleatum subsp. polymorphum’s genome revealed the presence of a putative flavodiiron protein (FDP) which is known to reduce O2 and/or NO to H2O or N2O, respectively. Colocalized with the FDP gene is a gene encoding a multicomponent enzyme called butyryl-CoA red…
has type: Thesis/Dissertation
date issued: 2025-02
is shown at: 10.14288/1.0447284
language: eng
degree discipline: Biochemistry and Molecular Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Wolthers, Kirsten
type: Text
identifier URI: http://hdl.handle.net/2429/89672