The biosynthesis of spermidine. Part 1: biosynthesis of spermidine from L-[3,4-13C2]methionine and L-[2,3,3-2H3]methionine

Abstract

Three mechanisms are discussed for the biosynthesis of spermidine from butane-1,4-diamine and decarboxylated adenosylmethionine catalysed by spermidine synthase: (i) enzyme-mediated S_N2 attack of butane-1,4-diamine at the aminopropyl group of decarboxylated adenosylmethionine; (ii)S_N2 attack at the aminopropyl group by a nucleophilic group of the synthase, to give an aminopropylated enzyme, which reacts with butane-1,4-diamine to give spermidine (double S_N2 displacement); and (iii) enzyme-induced intramolecular closure of decarboxylated adenosylmethionine to give protonated azetidine, which reacts with butane-1,4-diamine to give spermidine (alternative double S_N2 displacement).

Using n.m.r. spectroscopy to determine isotope distributions in spermidines derived from Escherichia coli fed on [3,4-¹³C₂]methionine and [2,3,3-²H₃]methionine, mechanisms (i) and (ii) are shown to be tenable, but mechanism (iii) is eliminated from consideration.