Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774295
Title: Studies on a mycolic acid reductase in Mycobacterium tuberculosis
Author: Javid, Asma
ISNI:       0000 0004 7961 5015
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2019
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Abstract:
Mycolic acids are essential components of the unique, lipid rich cell wall of M. tuberculosis. However, enzymes involved in the biosynthesis of mycolic acids remain under exploited as drug targets despite one of the early and hallmark anti-TB drug isoniazid which inhibits mycolate biosynthesis. Previous studies from our laboratory identified mycolate processing enzymes and transporters. A mycolyl reductase was identified to play a role in the final reduction step in mycolic acid biosynthesis in Mycobacterium smegmatis and Corynebacterium glutamicum. Using gene knockdowns I have now extended these studies to slow growing mycobacteria like Mycobacterium tuberculosis and Mycobacterium bovis BCG. The results in this thesis clearly indicated that the mycolyl reductase Rv2509 involved in the final stages of mycolic acid biosynthesis is essential in M.tuberculosis and M.bovis BCG. Furthermore using BLAST-P alignments and predictions of a 3D structure we identified unique domains and residues in the mycolate processing enzymes, and present functional studies on the same. This unique domain and other residues identified from in silico analysis of the structure of Rv2509 were important for the functionality of the protein following complementation studies. Purification of the protein of Rv2509 led to the identification of the possible substrate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.774295  DOI: Not available
Keywords: QH301 Biology
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