The chemical reactions resulting in the formation of deoxyhypusine from spermidine by the enzyme [eIF-5A]-deoxyhypusine synthase. The reaction occurs in four steps: 1. spermidine + NAD+ = dehydrospermidine + NADH + H+; 2. dehydrospermidine + [enzyme]-lysine = 1,3-diaminopropane + [enzyme]-lysine-N6=CH(CH2)3NH2; 3. [enzyme]-lysine-N6=CH(CH2)3NH2 = [eIF-5A]-lysine-N6=CH(CH2)3NH2; 4. [eIF-5A]-lysine-N6=CH(CH2)3NH2 + NADH + H+ = [eIF-5A]-deoxyhypusine + NAD+.