The goals of my research are the discovery and characterization of biologically active novel natural products from marine microorganisms.
Historically natural products have played an enormous role in the pharmaceutical industry, with compounds such as penicillin, vancomycin and taxol being used clinically as antibiotics and cancer chemotherapeutics. Due to increased levels of resistance to chemotherapies there is a continual need for the discovery of new natural products with novel mechanism of actions against disease. In our lab we focus on the tremendous microbial diversity of the marine environment with a particular focus on bacteria isolated from deep-water marine sediments as a source of new compounds.
This research is accomplished by a combination of marine microbiology, fermentation science, high-throughput screening and analytical and synthetic chemistry:
a) Marine microbiology and fermentation science: development of techniques for the isolation and genetic characterization of novel bacteria, improvement in fermentation conditions, exploration of microbial co-culture for induction of secondary metabolite production. b) High-throughput screening: It is crucial to focus on new chemical compounds with interesting biological activity. We are actively involved in screening our extract libraries in the UTSW high-throughput screening facility as well as our own screens for antibiotic and antifungal activity. c) Analytical Chemistry: The critical step in the microbial drug discovery process is the isolation and structural determination of the active compounds. This is accomplished by the combination of HPLC, MS, NMR (1D and 2D) and synthetic chemistry. The recent addition of an LC-SPE-NMR system will allow us to develop new techniques for the rapid identification of novel natural products. d) Synthetic Chemistry: Synthetic manipulation of biologically active natural products will allow us to determine structure activity relationships (SAR) to improve the potential therapeutic use of newly discovered compounds.
We believe this multi-disciplinary approach to natural product drug discovery will led to new chemical structures with novel mechanism of actions and eventually be used clinically for the treatment of disease.
RESEARCH INTERESTS
natural products
marine microbiology
organic chemistry
analytical chemistry
RECENT PUBLICATIONS
MacMillan, J.B.; Skepper, C.; Zhou, G.Z.; Skepper, C.; Masuno, M.N.; Molinski, T.F., "Chlorocyclopropane Macrolides from the Marine Sponge Phorbas sp. Assignment of Configurations of Phorbasides A and B by Quantitative CD" J. Am. Chem. Soc, 2007
MacMillan, J.B.; Linington, R.G.; Andersen, R.J.; Molinski, T.F., "Stereochemical Assignment in Acyclic Lipids Across Long Distance by Circular Dichroism: Absolute Stereochemistry of the Aglycone of Caminoside A" Angewandte Chemie International Edition, 43:5946-5951, 2004
MacMillan, J.B.; Molinski, T.F, "Long-Range Stereo-Relay: Relative and Absolute Configuration of 1,n-Glycols from Circular Dichroism of Liposomal Porphyrin Esters" J. Am. Chem. Soc., 126:9944-9945, 2004
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