Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2 (eEF-2).

Dipthamide is named after the toxin produced by the bacterium Corynebacterium diphtheriae, which targets diphthamide.

[1][3] Diphthamide is biosynthesized from histidine and S-adenosyl methionine (SAM).

The whole synthesis takes place in three steps:[1] In eukaryotes, this biosynthetic pathway contains a total of 7 genes (Dph1-7).

[1] The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways.