Virginia Tech Life Science Seminar Series
Dr. Joseph Jarrett on "Radical Enzymes Involved in Sulfur Metabolism: How Biotin is Formed Using Iron-Sulfur Clusters and Radical Chemistry"
Friday, December 5, 12:20pm, VBI Conference Center, located at Life Science Circle
Abstract: The biosynthetic pathways for several sulfur-containing biomolecules require the substitution of sulfur for hydrogen at unreactive carbon atoms. Examples include biotin, lipoic acid, methylthioether modifications found in some nucleic acids and proteins, and thioether crosslinks found in peptide natural products. Enzymes that employ radical chemistry play a crucial role in these difficult bond-forming reactions. Radical S-adenosyl-L-methionine (SAM) enzymes use an iron-sulfur cluster to catalyze the reduction of SAM to methionine and a highly reactive 5′‑deoxyadenosyl radical; this radical can abstract hydrogen atoms from otherwise unreactive carbon-hydrogen bonds, facilitating the introduction of a variety of functional groups. Biotin synthase also contains a second iron-sulfur cluster and uses radical chemistry to insert a sulfur atom from this cluster into the precursor dethiobiotin, generating the thioether ring of the cofactor as the last step in the biosynthetic pathway. The use of radical chemistry involving iron-sulfur clusters is an efficient anaerobic route to the generation of carbon-sulfur bonds in cofactors, secondary metabolites, and other natural products.