A lecture by Dr. Squire Booker. A new and menacing mechanism for antibiotic resistance is on the rise, involving the C8 methylation of adenosine 2503 of 23S rRNA of the bacterial ribosome. Indeed, this seemingly minor addition, installed by the radical SAM protein, Cfr, impedes the binding of over five classes of antibiotics to their targets. Considering that one half of all antibiotics currently in use target the bacterial ribosome, this emerging mechanism of resistance has the potential to severely reduce the effectiveness of the world’s current arsenal of antibiotics. Interestingly, C8 of adenosine is chemically resistant to biological methylation by all currently accepted mechanisms, which usually involves the attack of a nucleophile onto an electrophilic methylating agent. This lecture will detail a new and novel strategy for the biological methylation of sp2-hybridized carbon centers, which involves radical intermediates generated via the reductive cleavage of S-adenosylmethionine and the participation of five essential cysteinyl residues.

Dr. Squire J. Booker is an Evan Pugh Professor of Chemistry and of Biochemistry and Molecular Biology at The Pennsylvania State University and holds the Eberly Family Distinguished Chair in Science. He is also an Investigator at the Howard Hughes Medical Institute.