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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 thesis is currently under Embargo and not available
Appears in Collections:Research Theses

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