Susan Wang, PhD

Associate Professor
Department of Biochemistry
School of Medicine

Research Information

Research Interests

The radical SAM (S-adenosyl-L-methionine) enzyme superfamily was initially described in 2001. The members of this superfamily, numbering in the thousands, catalyze a wide variety of reactions, most of which have not been characterized. The few radical SAM enzymes that have been studied share only two obvious characteristics. 1 - They each contain an unusual iron-sulfur ([4Fe-4S]) cluster in which three ligands to the cluster are cysteine residues from the protein, while the fourth ligand is SAM. These cysteine residues are found in a CXXXCXXC amino acid motif considered to be the hallmark of this superfamily. 2 - They utilize a 5'-deoxyadenosyl (Ado-CH2) radical generated from the homolytic cleavage of SAM to abstract a hydrogen atom from the appropriate substrate. Our lab is interested in the fundamental mechanistic issues surrounding the subfamily of radical SAM enzymes believed to catalyze interesting and difficult methyl transfer reactions required by some organisms for antibiotic biosynthesis. Little is understood about these enzymes, but like many other methyltransferases, they reportedly require methylcobalamin (a derivative of vitamin B12) for activity. Since either SAM or methylcobalamin can function as a methyl transfer agent, we wish to determine whether these proteins require one or both as cofactors (or perhaps substrates) in catalysis. We combine a variety of techniques spanning molecular biology, organic synthesis, nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopies, and protein chemistry. These studies will provide further insight into the biological pathways used for antibiotic synthesis, thus facilitating the design of new antibiotic compounds and leading to the improvement of industrial processes used for large-scale antibiotic production.

Publications

View Publications

  • Sha, Z., Fishovitz, J., Wang, S., Chilakala, S., Xu, Y., and Lee, I.
    "A Selective Fluorogenic Peptide Substrate for the Human Mitochondrial ATP‐Dependent Protease Complex ClpXP". ChemBioChem 21(14):2037-2048 (2020)
  • Wang S.C.
    “Cobalamin-dependent radical S-adenosyl-l-methionine enzymes in natural product biosynthesis.”
    Nat Prod Rep. 35(8):707-720 (2018)
  • Hu K., Werner W.J., Allen K.D., Wang S.C.
    “Investigation of enzymatic C-P bond formation using multiple quantum HCP nuclear magnetic resonance spectroscopy.”
    Magn Reson Chem. 53(4):267-72 (2015)
  • Allen K.D., Wang S.C.
    “Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217.”
    Biochim Biophys Acta. 1844(12):2135-44 (2014)
  • Allen K.D., Wang S.C.
    “Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis. ”
    Arch Biochem Biophys. 543:67-73 (2014)
  • Werner W.J., Allen K.D., Hu K., Helms G.L., Chen B.S., Wang S.C.
    “In vitro phosphinate methylation by PhpK from Kitasatospora phosalacinea. ”
    Biochemistry. 50(42):8986-8 (2011)

Education

PhD
University of Texas
Post Doc
University of Wisconsin