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Type: Thesis
Title: Development of New Antibiotics Based on Biotin Biology
Author: Lee, Kwang Jun
Issue Date: 2019
School/Discipline: School of Physical Sciences
Abstract: PARTIAL ABSTRACT: Biotin is an essential vitamin that is required for growth and pathogenicity of bacteria. Biotin protein ligase (BPL) catalyses the ordered reaction of biotin and ATP to give biotinyl-5̕´-MP, which then activates a number of biotin dependent enzymes that are critical to cell survival. Dethiobiotin synthase (DTBS) is the sole enzyme responsible for catalysing a key step in biotin biosynthesis, namely the carboxylation of 7,8-diaminopelargonic acid (DAPA), closing the ureido ring to form dethiobiotin in a reaction requiring a nucleotide triphosphate. Research undertaken in this thesis highlights strategies to selectively inhibit Staphylococcus aureus biotin protein ligase (SaBPL) using 1,2,3-triazole and sulfonamide isosteres to replace the phosphoroanhydride linker found in biotinyl-5´-AMP. In addition, this thesis discusses the design and development of inhibitors targeting Mycobacterium tuberculosis dethiobiotin synthase (MtbDTBS).
Advisor: Abell, Andrew
George, Jonathan
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 2019
Keywords: Antibiotic
biotin protein ligase
dethiobiotin synthase
enzyme inhibitor
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
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