Many Paths to Homospermidine Synthesis♦

♦ See referenced article, J. Biol. Chem. 2010, 285, 14711–14723

Polyamines are small organic polycations that are universally distributed in bacteria, archaea, and eukaryotes. During the course of evolution, however, the biosynthetic strategy for polyamine production has branched out into multiple parallel and intersecting pathways. The triamines spermidine and norspermidine, for example, have known alternate pathways of synthesis, and in this Paper of the Week, Frances Shaw and colleagues sought to determine the evolution of homospermidine synthesis, a predominant bacterial polyamine, and look for alternate pathways. A close sequence analysis revealed that the homospermidine synthase (HSS) enzyme is structurally similar to lysine metabolic enzymes and likely evolved from carboxyspermidine dehydrogenase, an enzyme responsible for alternative spermidine biosynthesis in diverse bacteria. They also demonstrated that HSS evolved vertically, primarily in α-Proteobacteria, although a diverse set of HSS orthologues spread by horizontal gene transfer to other bacteria, archaea, viruses, and eukaryotes. Although homospermidine was required for normal growth of the α-proteobacterium Rhizobium leguminosarum, both spermidine and norspermidine could restore growth of polyamine-depleted bacteria, suggesting that exact symmetry or carbon backbone length is not critical for polyamine function in growth. Finally, Shaw and colleagues found that some bacteria species lacking HSS can still synthesize homospermidine; all these bacteria contained deoxyhypusine synthase orthologues, which suggests they synthesize homospermidine similar to the alternative pathway found in some plants.

Structural comparison of homospermidine synthase (B) with related proteins aspartate dehydrogenase (A), lysine 6-dehydrogenase (C), and saccharopine reductase (D); the NAD⁺ and NADPH cofactors are shown in black.