Studies on the Biosynthesis of Nucleocidin in Streptomycetes

Approximately 80% of currently used antibiotics were first discovered from Streptomyces. In addition, many pharmaceuticals, including antibiotics, are halogenated. In particular about a quarter of the top-selling pharmaceuticals are fluorine-containing compounds. The overall objective of my doctoral thesis is to elucidate the complete biosynthetic pathway of the fluorinated antibiotic, nucleocidin, in Streptomyces. Elucidating the biosynthesis of nucleocidin, will be greatly advantageous in helping future research in finding new fluorinated and bioactive natural products through genome mining. As well, the nucleocidin fluorinase can be developed for applications in fluorinating pharmaceutical compounds, offering a greener and more specific alternative to synthetic fluorination methods. My PhD thesis has four goals: 1) Identification of new and higher titre Streptomyce producers of nucleocidin, 2) Identify the minimal set of genes in Streptomyces necessary for nucleocidin biosynthesis, 3) characterize the encoded enzymes that synthesize the sulfamate moiety, 4) characterize the encoded enzyme(s) which catalyze fluorination. During this internship, I will focus on completing the second goal. I have identified key genes to focus on for gene disruption experiments to determine which genes in Streptomyces are necessary for nucleocidin biosynthesis.

Faculty Supervisor:

David Zechel

Student:

Partner:

Albert-Ludwigs-Universität Freiburg

Discipline:

Life Sciences

Sector:

Education

University:

Queen's University

Program: