Multiple antibiotic resistant bacteria continue to be a threat to the health of the world's population. Glycopeptide antibiotics are one type of drug that are used to treat these serious pathogens. Increased usage over the years has led to the emergence of bacteria which are resistant to these glycopeptide antibiotics and now the need for altered antibiotics with an increased effectiveness has arisen. 𝘚𝘵𝘳𝘦𝘱𝘵𝘰𝘮𝘺𝘤𝘦𝘴 𝘵𝘰𝘺𝘰𝘤𝘢𝘦𝘯𝘴𝘪𝘴 NRRL 15009 produces the glycopeptide antibiotic A47934. Here, the biosynthetic gene cluster for A47934 was sequenced in its entirety. All enzymes encoded by assigned open reading frames were analyzed and functions assigned where possible. The resulting biosynthesis cluster encodes all the enzymes necessary to produce A47934, as well as confer resistance and regulate the resistance response. In addition to sequencing the biosynthetic gene cluster, enzymatic studies were attempted on the two-component regulatory system (VanR and VanS) which confers resistance to A47934. Finally, inactivation of 𝘴𝘵𝘢𝘓 was attempted. Overall, the results presented here should help us to further understand how these chemically complex glycopeptide antibiotics are made and lend further insight into how we can attempt to produce new semi-synthetic versions. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22846 |
| Date | January 2002 |
| Creators | Pootoolal, Jeffrey |
| Contributors | Wright, G. D., Biochemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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