nonprotein amino-acid biosynthesis protein modification peptidyl-diphthamide biosynthesis PMID:6402493 PMID:16648478 UPa:UPA00559 2'-(3-carboxamido-3-(trimethylammonio)propyl)-L-histidine biosynthesis GO:0017183 pathway PMID:15485916 The translation elongation factor 2 (eEF-2) in eukaryotes and some archaea contains a unique posttranslationally modified histidine residue, termed diphthamide, which serves as the only target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A. The biosynthesis of diphthamide represents one of the most complex posttranslational modifications. The biosynthesis is accomplished by stepwise additions to the His715 (His699 in yeast) residue of eEF-2.