Bacterial carboxyspermidine route to spermidine

A bacterial two-reaction route that converts putrescine and L-aspartate 4-semialdehyde to spermidine. NADPH-dependent carboxyspermidine dehydrogenase first forms carboxyspermidine, which a PLP-dependent decarboxylase converts to spermidine and carbon dioxide. The route draws its added carbon unit from aspartate metabolism rather than decarboxylated S-adenosylmethionine. It occurs across multiple bacterial lineages, but neither universal occurrence nor universal exclusion of other polyamine routes is implied. Related family members differ in substrate preference and can support norspermidine, tetraamine or agmatine-series chemistry; membership alone does not establish this putrescine route. Substrate supply, transport and downstream polyamine effects lie outside the two-reaction boundary.

This is a concrete, chemically specified two-step pathway with family selectors and grounded representatives, not a claim that every bacterial genome realizes it. Bacteria is the shared taxon context; the positive or inferred representatives sample Pseudomonadota, Campylobacterota and Bacteroidota. Bacillota Clostridium proteins were reviewed as specificity comparators, not presented as a proven native putrescine-route pair. Neither adjacency nor essentiality is universal: Campylobacter and Helicobacter candidates are not adjacent, and C. jejuni 81116 CASDH deletion increases spermidine. C. jejuni 81116 and NCTC 11168 are separate targets. The Helicobacter 26695 CASDH sequence-start discrepancy prevents use as a direct structural exemplar. The paired pathway can coexist with other polyamine machinery; inactive H. pylori SpeE is a target-specific negative result, not a general exclusion rule. GO:0102143 names carboxynorspermidine dehydrogenase but explicitly includes carboxyspermidine oxidation to putrescine; the reductive reaction used here is RHEA:34111. No current reaction-specific CASDC GO term was established, so the second leaf names the precise RHEA:34095 activity without substituting broad carboxy-lyase as the claimed reaction. Gene reviews propose the missing term. PANTHER SF2 and SF1 identities are membership filters, not substrate proofs; Synechocystis and Clostridium CAPA chemistry shows why functional restriction is necessary. No PAINT ancestral node is asserted: the dehydrogenase family lacks a suitable functional node and the decarboxylase family node concerns LysA. The same-family CAPA route needs a third enzyme and remains outside this module; alternative diamine inputs and onward tetraamine production are also outside this exact reaction boundary.