Deoxyhypusine synthase (DHS) is involved in the post-translational activation of the eukaryotic initiation factor 5A (eIF5A) and, as a side-reaction, catalyzes the formation of homospermidine if its substrate, the eIF5A precursor protein, is replaced by putrescine. Plant homospermidine synthase is assumed to be phylogenetically derived from DHS; it represents a DHS having lost its intrinsic activity. The enzyme is expressed in plants producing pyrrolizidine alkaloids where it catalyzes the formation of homospermidine the unique precursor of pyrrolizidine alkaloids. Here we show that 29 species randomly selected from 18 angiosperm families as well as a few other terrestrial plant species, all were able to produce small amounts of homospermidine. Basing on these results and in the context of literature on the occurrence of homospermidine in the organismic kingdoms, a universal occurrence of homospermidine is assumed and ubiquitous DHS is suggested to be responsible for its formation. The synthesis of homospermidine as an enzymatic by-product of an essential enzyme is discussed in respect to the evolutionary origin of homospermidine synthase and the biosynthetic pathway of pyrrolizidine alkaloids.