New routes for spermine biosynthesis.

Abstract

The polyamine spermine is a flexible linear teraamine found in bacteria and eukaryotes, and in all known cases is synthesized from triamine spermidine by addition of an aminopropyl group acquired from decarboxylated S-adenosylmethionine (dcAdoMet). We have now identified in bacteria a second biosynthetic route for spermine based on the formation of carboxyspermine from spermidine, dependent on aspartate β-semialdehyde (ASA). This route also produces thermospermine from spermidine via carboxythermospermine. Two enzymes, carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase, are responsible for ASA-dependent production of spermidine, spermine and thermospermine from diamine putrescine. Production of spermine/thermospermine from spermidine is controlled primarily by carboxyspermidine dehydrogenase, not carboxyspermidine decarboxylase. This new ASA-dependent spermine biosynthetic pathway is an example of convergent evolution, employing nonanalogous, nonhomologous enzymes to produce the same biosynthetic products as the dcAdoMet-dependent spermine pathway. We have also identified bacteria that encode hybrid spermine biosynthetic pathways dependent on both dcAdoMet and ASA. In the hybrid pathways, spermidine is produced from agmatine primarily by the ASA-dependent route, and spermine is synthesized from agmatine or spermidine by dcAdoMet-dependent modules. Both parts of the hybrid pathway initiate from agmatine and each produces N¹-aminopropylagmatine, so that agmatine, N¹-aminopropylagmatine and spermidine are common, potentially shared metabolites. Bacteria such as Clostridium leptum that encode the hybrid pathway may explain the origin of spermine produced by the gut microbiota. This is the first example of convergent evolution of hybrid dcAdoMet- and ASA-dependent N¹-aminopropylagmatine, spermidine and spermine biosynthesis encoded in the same genomes, and suggests additional polyamine biosynthetic diversification remains to be discovered.