Date of Award


Document Type


Degree Name

Master of Science (MS)


Department of Chemistry

First Advisor

Jon Friesen


Infectious diseases, with increasing prevalence of antibiotic resistant bacteria, coupled with the declining rate in discovery of antimicrobial agents, impose one of the most significant threats to human health. Here we identify 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (CMS) as a valid target for antibiotic development which is an enzyme in pathogenic organisms that leads to the biosynthesis of isoprene precursor molecules. Isoprene molecules are one of nature’s most common building blocks that are vital to many biological metabolic processes and are synthesized via the mevalonic acid dependent (MVA), or methylerythritol phosphate (MEP) pathway. Vertebrates utilize the MVA pathway, while many pathogenic bacteria use the MEP pathway for isoprenoid biosynthesis. With separate pathways expressed between vertebrates and bacteria, the MEP pathway is an attractive target for the development of effective novel antimicrobial therapeutics. This report kinetically characterizes two putative isoforms of CMS from Listeria monocytogenes. This study validates a previously developed high performance liquid chromatography (HPLC) method for the kinetic characterization of cytidylyltransferase enzymes. Structural homology and sequence analysis of both putative isoforms of CMS provide new evidence suggesting the lmo0235 gene encodes a CMS and the lmo1086 gene from Listeria monocytogenes encodes a putative ribitol 5-phosphate cytidylyltransferase.


Imported from ProQuest Oblazny_ilstu_0092N_11105.pdf


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