Strongly supported carboxyspermidine dehydrogenase candidate. PP_2928 is adjacent to nspC and belongs to the CASDH/CANSDH family. Comparative, domain, and synteny evidence predicts NADPH-dependent condensation of putrescine with aspartate semialdehyde to form carboxyspermidine; direct biochemical or genetic confirmation in KT2440 is not available.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0102143 carboxynorspermidine dehydrogenase activity | ISS file:projects/P_PUTIDA/deep-research/PSEPK__bacterial-carboxyspermidine-biosynthesis__ppu00330-deep-research-openscientist.md | NEW | Summary: Family, domain, protein-length, and nspC synteny evidence support CASDH/CANSDH activity, but no direct KT2440 assay is available. GO:0102143 has the current label "carboxynorspermidine dehydrogenase activity"; with putrescine as substrate, this family activity yields carboxyspermidine and is referred to as CASDH in this pathway. Reason: This is an inherited comparative proposal, not a newly measured KT2440 function. PMID:37878710 and PMID:40074085 show substrate and pathway diversification in related proteins, so family membership and adjacency do not by themselves prove native putrescine preference. The curated-rule/comparative pathway inference is retained, with physiological substrate identity explicitly open. Supporting Evidence: file:PSEPK/PP_2928/PP_2928-uniprot.txt PANTHER; PTHR43796:SF2; CARBOXYNORSPERMIDINE SYNTHASE PMID:19196710 it increasingly uses putrescine as a substrate and forms carboxyspermidine, which is then converted to spermidine by CANSDC PMID:36283333 CASDH condenses putrescine and aspartate Ξ²-semialdehyde into carboxyspermidine in an NADPH-dependent manner. file:PSEPK/PP_2928/PP_2928-deep-research-openscientist.md |
| GO:0008295 spermidine biosynthetic process | ISS file:projects/P_PUTIDA/deep-research/PSEPK__bacterial-carboxyspermidine-biosynthesis__ppu00330-deep-research-openscientist.md | NEW | Summary: Adjacency to nspC and comparison with characterized bacterial pathways strongly support participation in the carboxyspermidine route to spermidine; this target-species pathway assignment remains inferential. Reason: This is an inherited comparative proposal, not a newly measured KT2440 function. PMID:37878710 and PMID:40074085 show substrate and pathway diversification in related proteins, so family membership and adjacency do not by themselves prove native putrescine preference. The curated-rule/comparative pathway inference is retained, with physiological substrate identity explicitly open. Supporting Evidence: file:PSEPK/PP_2928/PP_2928-uniprot.txt PANTHER; PTHR43796:SF2; CARBOXYNORSPERMIDINE SYNTHASE PMID:19196710 deletion of either CANSDC or the putative CANSDH led to loss of sym-norspermidine and spermidine PMID:22025614 Orthologues encoding carboxyspermidine dehydrogenase and carboxyspermidine decarboxylase are found clustered with an array of diverse putrescine biosynthetic genes in different bacterial genomes, consistent with a role in spermidine, rather than sym-norspermidine biosynthesis. |
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Download this section (compressed HTML)Q: Does purified PP_2928 preferentially produce carboxyspermidine from putrescine under physiological conditions?
Experiment: Assay the purified PP_2928/NspC pair across putrescine, 1,3-diaminopropane and agmatine-derived substrates, identify products by LC-MS, and measure polyamines after deletion and complementation in KT2440. Distinguish catalytic capacity from native substrate use and flux.
Type: biochemical validation
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: PP_2928 has not been tested biochemically or genetically in KT2440, so its substrate preference and contribution to cellular spermidine production remain unconfirmed.
OPEN BIOLOGY
What is known: Exact PTHR43796:SF2 family membership, adjacency to nspC, and characterized orthologous CASDH/CANSDH pathways strongly support the assignment. Related family members can instead use agmatine or participate in onward tetramine synthesis; those activities are not established for this KT2440 pair.
Significance: Direct validation would establish whether carboxyspermidine is the physiological product in KT2440.
What would resolve it: Assay the purified PP_2928/NspC pair across putrescine, 1,3-diaminopropane and agmatine-derived substrates, identify products by LC-MS, and measure polyamines after deletion and complementation in KT2440. Distinguish catalytic capacity from native substrate use and flux.
Provenance (the field's own admissions):
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