Faculty Research
Alphabetical · By research area

Understanding the chemistry by which Nature assembles biological molecules is not only an exciting intellectual endeavour, but is also a prerequisite to rationally influence life processes in medicine and agriculture. Our research currently centers on the formation of important biological molecules, including antimicrobial peptides, amino acid metabolites, and polyketides. The approach is interdisciplinary. Experimental aspects of our projects encompass organic synthesis and spectroscopic methodology (especially NMR and mass spectrometry), as well as isotopic techniques, natural products isolation, enzymatic reactions, and culturing of microorganisms. Current projects include:

• Investigation of the three dimensional structure, mechanism of action, formation and applications of bacteriocins from lactic acid bacteria. These antimicrobial peptides (37-56 amino acids) are non-toxic to mammals, naturally preserve food, and may be useful for treatment of gastrointestinal diseases.
• Examination of the mechanism of polyketide biosynthesis in fungi, especially formation of lovastatin (a widely-prescribed cholesterol-lowering drug) and generation of biologically active macrolides
• Construction of structurally modified neuropeptide hormones and their antagonists to provide improved activity and stability. These compounds influence a host of biological processes including lactation, childbirth, pain, appetite, pigmentation, pheromone biosynthesis and embryonic development.
• Understanding and duplicating the mechanisms of unusual enzymes, especially amino acid epimerases and hydroxylases (e.g. P450 and ketoglutarate dependent oxygenases).

A preferred conformation of the precursor for Carnobacteriocin B2, a non-toxic antimicrobial peptide that contains 48 amino acids and is produced naturally in meat products by Carnobacterium piscicola. The red arrow indicates the site of proteolytic cleavage that produces the mature bacteriocin (bottom portion).

Selected Publications

Liu, W.; Chan, A.S.H.; Liu, H.; Cochrane, S.A.; and Vederas, J.C. Solid Supported Chemical Syntheses of Both Components of the Lantibiotic Lacticin 3147. J. Am. Chem. Soc. 2011, 133, 14216-14219.

Sit, C.S.; Van Belkum, M.J.; McKay, R.T.; Worobo, R.W.; and Vederas, J.C. The 3D solution structure of thurincin H, a bacteriocin with four sulfur to α-carbon crosslinks. Angew. Chemie Int. Ed. 2011, 123, 8877-8880.

Barriuso, J.; Nguyen, D.T.; Li, J. W.-H; Roberts, J.N.; MacNevin, G.; Chaytor, J.L.; Marcus, S.L.; Vederas, J.C.; and Ro, D.-K. Double Oxidation of the Cyclic Nonaketide Dihydromonacolin L to Monacolin J by a Single Cytochrome P450 Monooxygenase, LovA. J. Am. Chem. Soc. 2011, 133, 8078-8081.

Van Belkum, M.J.; Martin-Visscher, L.M.; and Vederas, J.C., Structure and genetics of circular bacteriocins. Trends Microbiol. 2011, 19, 411-418.

Liu, H.; Boudreau, M.A.; Zheng, J.; Whittal, R.M.; Austin, P.; Roskelley, C.D.; Roberge, M.; Andersen, R.J. and Vederas, J.C. Chemical Synthesis and Biological Activity of the Neopetrosiamides and Their Analogues: Revision of Disulfide Bond Connectivity. J. Am. Chem. Soc. 2010, 132, 1486–1487.