The US FDA-approved proteosome inhibitor carfilzomib (derived from the natural product epoxomicin; Supplementary table ) contains an epoxyketone moiety which undergoes both epoxide ring opening and cyclocondensation with the N-terminal threonine residue of the 20S proteosome to form a morpholine ring ; the combination of reactions renders inhibition irreversible. The antibiotic fosfomycin inhibits UDP N-acetylglucosamine enolpyruvyl transferase by reacting with Cys115 and preventing transfer of phosphoenolpyruvate.