The continued propagation of antibiotic resistance requires the development of new therapeutics. The lipopeptide antibiotic enduracidin has demonstrated high activity against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus. In addition to a lack of cross-resistance with existing antibiotic classes, enduracidin has no known transferrable resistance mechanism. The development of enduracidin as...
Molecular genetic and enzymological techniques have been employed to study secondary metabolite biosynthesis. These investigations have focused on two projects: the cloning and heterologous expression of biosynthetic gene clusters from unculturable marine organisms and the characterization of individual enzymes involved in the biosynthesis of the antifungal agent blasticidin S. The...
F1FO-ATP synthase targeting antimicrobials apoptolidin 1 (A1), (+)-erythromefloquine,
and oligomycin were tested in vitro for synergistic minimum inhibitory
concentrations against Staphylococcus aureus. Synergy was strictly defined as inhibition
by at most 25% the MIC of each participating drug. Ampicillin, with an MIC of 0.8
ug/mL, served as a negative control....
L-pipecolic acid (L-PA) is the higher homolog of proline. It occurs naturally in
many organisms, including primates, as an intermediate in lysine degradation. The
pathway by which lysine is converted into L-pipecolic acid employs the enzyme Lpipecolate
oxidase (L-PO), and appears to be tissue specific to the central nervous system...
Molecular genetic and enzymological techniques have been employed to study antibiotic biosynthesis. The nonproteinogenic amino acid capreomycidine is the signature residue found in the tuberactinomycin family of antitubercular peptide antibiotics and an important element of the pharmacophore. Recombinant VioG, a single module peptide synthetase from the viomycin gene cluster cloned...
Dental disease is a very prevalent and costly disease in which the symptoms, not the disease, are currently being treated. The disease is caused by pathogenic oral bacteria, many of which are a part of the Mutans Streptococci. The objective of this thesis was to find a natural substance that...
Molecular genetic and enzymological techniques have been employed to study antibiotic biosynthesis. In this thesis, we studied the formation and modification of the nonproteinogenic amino acid enduracididine (End), which exists in two important antibiotics, mannopeptimycins (MPPs) and enduracidin.
Sequence analysis of the MPP gene cluster revealed that the product of...