Shaun Lee, Ph.D.

Address :
University of California, San Diego
Leichtag Room 283
9500 Gilman Drive, 0721
La Jolla, CA 92093-0721

Email : swl004@ucsd.edu

Phone : 858-822-0684
Fax : 858-822-5888



I am a postdoctoral fellow under the Heme and Blood Proteins Training Grant in the department of Chemistry and Biochemistry. My current project focuses on the biosynthetic pathway of a class of ribosomally-encoded antibiotic toxins that are produced by a wide array of microorganisms. These microorganisms contains a cluster of genes encoding a precursor to the peptide antibiotic, as well as three proteins that function in concert to post-translationally convert the precursor into the active antibiotic. We have discovered that this cluster of genes is present in diverse phyla, including gram-positive and gram-negative bacteria, Cyanobacteria, and Archaea. These gene clusters are also present in several important human pathogens, such as E. coli, Streptococcus pyogenes, Staphylococcus aureus, Listeria monocytogenes, and Clostridium botulinum. In concert with Dr. Victor Nizet in the department of Pediatrics, we have validated the biosynthetic pathway of Streptolysin S by reconstituting its hemolytic activity in vitro using purified components of the precursor peptide and its modifying enzymes. It is likely that the discovery of similar peptidic antibiotics will rapidly expand as more genomes are sequenced. Our findings thus represent the first steps directed toward the discovery of an entirely new class of antibiotics. This is highly relevant given the rapid emergence of antibiotic resistance mechanisms in bacteria. Importantly, these new peptide antibiotics are produced ribosomally, and thus are amenable to genetic engineering strategies.



Publications

1. Mitchell, D.A.; Lee, S.W.; Pence, M.A.; Markley, A.L.; Limm, J.D.; Nizet, V.; Dixon, J.E., "Structural and functional dissection of the heterocyclic peptide cytotoxin streptolysin S" J. Biol. Chem. 284(19):13004-12. (2009)
   
   
2. Lee, S.W.* and Mitchell, D.A.*, Markley, A.L., Hensler, M.E., Gonzalez, D., Wohlrab, A., Dorrestein, P.C., Nizet, V., Dixon, J.E., “Discovery of a Widely Distributed Toxin Biosynthetic Gene Cluster” Proc. Natl. Acad. Sci. USA, 105: 5879-5884 (2008)
   * These authors contributed equally to this work
   
   Commentary: Walsh, C.T.; Nolan, E.M., “Morphing Peptide Backbones into Heterocycles” Proc. Natl. Acad. Sci. USA, 105: 5655-5656 (2008)
   
   Faculty of 1000 Biology Evaluation: Roepe, P., Exceptional rating factor
   http://www.f1000biology.com/article/id/1104904/evaluation
   
   
3. Higashi, D.L., Lee, S.W., Snyder, A., Weyand, N.J., Bakke, A, So, M. Dynamics of Neisseria gonorrhoeae attachment: microcolony development, cortical plaque formation, and cytoprotection. 2007. Infect Immun. Oct;75(10):4743-53.
   
   
4. Yooseph S., Sutton G, Rusch DB, Halpern AL, Williamson SJ, Remington K, Eisen JA, Heidelberg KB, Manning G, Li W, Jaroszewski L, Cieplak P, Miller CS, Li H, Mashiyama ST, Joachimiak MP, van Belle C, Chandonia JM, Soergel DA, Zhai Y, Natarajan K, Lee S, Raphael BJ, Bafna V, Friedman R, Brenner SE, Godzik A, Eisenberg D, Dixon JE, Taylor SS, Strausberg RL, Frazier M, Venter JC. The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families. 2007. PLoS Biol. Mar;5(3):e16.
   
   
5. Weyand, N., Lee, S.W., Yoshihara, P., and So, M. Involvement of the CD46 cytoplasmic isoforms Cyt1 and Cyt2 in TypeIV pilus-dependent Neisseria gonorrhoeae attachment to host cells. Infect Immun. Apr;74(4):2428-35 (2006).
   
   
6. Lee, S.W., Higashi, D.L., Snyder A., Merz, A.J., Potter, L., and So, M. PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells. Cell. Micro. 7(9):1271-84 (2005).
   
   
7. Lee, S.W., Bonnah, R.A., Higashi, D.L., Atkinson, J.P., Milgram, S.L., and So, M. CD46 is phosphorylated at tyrosine 354 upon infection of epithelial cells by Neisseria gonorrhoeae. J Cell Biol. 156(6):951-957 (2002).
   
   
8. Bonnah, R.A., Lee, S.W., Vasquez, B.L., Enns, C.A., and So, M. Alteration of Epithelial Cell Transferrin-iron Homeostasis by Neisseria meningitidis and Neisseria gonorrhoeae. Cell. Micro. 2:207-218 (2000).
   
   
9. Evengard, B., Briese, T., Lindh G., Lee, S., and W.I. Lipkin. Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome. J Neurovirol. 5(5):495-9 (1999).