Streptomyces Secondary Metabolism
A primary focus of the Shipley research group is the development of new pharmacologically active compounds using Streptomyces bacteria. Streptomyces bacteria are Gram positive soil-dwelling bacteria that are spectacular producers of secondary metabolites with useful medicinal activities. The secondary metabolism of an organism is the sum of all biosynthetic pathways that are present that are not required for viability or reproduction. Most interesting bioactive molecules fit into this metabolic subset. Our approach involves rationally modifying existing biosynthetic pathways to produce new, but related, structures either by introducing new biosynthetic genes or by supplementing cultures of bacteria where key genes have been deleted or interrupted by homologous DNA recombination.
Our primary research organism of interest is the asukamycin-producing bacterium Streptomyces nodosus ssp. asukaensis. Asukamycin is a member of the manumycin family of antibiotics, which exhibit a wide range of interesting activities, including potential as anti-tumour and anti-inflammatory agents. We hope to expand and improve the medicinal and biological activities found in this family by generating a library of related compounds by complementation of blocked mutants.
Mixture Profiling by Nuclear Magnetic Resonance (NMR) Spectrometry
Nuclear magnetic resonance (NMR) spectrometry measures the electronic environment around spin-active nuclei in a strong applied magnetic field. This allows us to determine a wealth of information about the local environment around that nucleus, including functional group information, and more interestingly, the presence of neighboring spin-active nucle. NMR has recently been found to be useful in the analysis of complex mixtures such as raw extracts of plants and microbes. NMR can be used to identify and quantify key components, or can be coupled with principal component statistical analysis to take more of a distance view. There is considerable opportunity in this field for new method development, and for the use of NMR to segregate samples by growing conditions, geographical regions, species or subspecies, or by extraction technique.
Structure Elucidation and Signal Assignment using Nuclear Magnetic Resonance Spectrometry
Using our 400 MHz NMR, our research team has the expertise and capacity to determine assignments and structural elucidation of unknown and interesting molecules. We apply this technique to generate structures for compounds isolated by guided fractionation of bioactive organisms, as well as confirmation and full assignment of polymers and macromolecules with useful physical properties.
There are currently openings for 2 students at the graduate level to pursue their degrees in Chemistry with research focused on NMR applications or bacterial secondary metabolism.
This page is maintained by Paul Shipley.