L-aspartate de novo and selected salvage routes to NAD+

A reusable, scope-limited route set for organisms that use the L-aspartate de novo pathway and/or selected nicotinate, nicotinamide, and NMN salvage alternatives. Every realization is end-to-end: NaMN made by L-aspartate de novo synthesis, PncB, or PncC must pass through deamido-NAD to NAD+, whereas NMN made by NAMPT must be adenylylated directly to NAD+. Alternative adenylyltransferase families and NAD synthetase nitrogen donors are modeled as variants. This is not a universal NAD+ biosynthesis hub: de novo synthesis through L-tryptophan and the kynurenine pathway is owned by the existing MODULE:kynurenine_nad_de_novo module and is not duplicated here. Nicotinate degradation, pyridine-nucleotide transhydrogenases, NAD kinase and NADP formation, NAD-consuming reactions, and unrelated aldehyde metabolism are outside the boundary.

MODULE:nad_biosynthesis_salvageDRAFTMetabolic Pathwaymodules/nad_biosynthesis_salvage.yaml
NAD+ biosynthetic processGO:0009435
file:modules/nad_biosynthesis_salvage-deep-research-openscientist.md
OpenScientist module research for L-aspartate de novo and selected NAD+ salvage
Provider research supplies literature-triage context for the reaction chemistry, NaMN/NMN distinction, enzyme-family alternatives, and nitrogen donors. Physical channeling, strict family-wide substrate exclusion, essentiality, and ancestral-history claims were not adopted. Route validity and requiredness are defined by the curated complete realizations in this YAML rather than by provider narrative.
file:projects/P_PUTIDA/deep-research/PSEPK__nad_biosynthesis_salvage__ppu00760-deep-research-openscientist.md
OpenScientist PSEPK ppu00760 NAD+ biosynthesis and salvage research
Provider research supplies taxon-specific literature-triage context for the seven supported KT2440 catalytic genes, broad-map exclusions, and the canonical PncA/NadV gap. Candidate transfer based only on a broad isochorismatase fold or single-copy framing is not accepted. PP_3298 was outside the ppu00760 candidate list and remains a separately grounded, unresolved CinA-C/PncC-family paralog.
file:modules/kynurenine_nad_de_novo.yaml
Existing kynurenine de novo NAD+ biosynthesis module
De novo NAD+ synthesis from L-tryptophan through the kynurenine pathway is modeled separately in MODULE:kynurenine_nad_de_novo. This route set does not duplicate that module or imply that L-aspartate is universal.
GO:0009435
NAD+ biosynthetic process
The route set comprises scoped alternatives that produce NAD+ de novo or from salvageable pyridine precursors.
GO:0034628
'de novo' NAD+ biosynthetic process from L-aspartate
The bacterial de novo segment converts L-aspartate to quinolinate and then to NaMN.
GO:0034355
NAD+ biosynthetic process via the salvage pathway
The salvage segment recycles nicotinate, nicotinamide, or NMN into an NAD+ precursor.
PMID:21953451
Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family.
PncC converts NMN to NaMN, allowing the product to enter the Preiss-Handler completion route.

The root requires one or more complete route classes; no empty realization is valid. All NaMN-producing alternatives are connected only to required NaMN adenylylation and deamido-NAD amidation, and NAMPT-produced NMN is connected only to required direct NMN adenylylation. PncA and PncC remain distinct: PncA deamidates nicotinamide to nicotinate, whereas PncC deamidates NMN to NaMN. The module deliberately ends at NAD+ and excludes kynurenine-route duplication, NADP formation, and NAD+ consumption. The KT2440-specific PP_3298 gap below is realization-level curation metadata; it neither changes the reusable route logic nor adds an obligatory family.

22Nodes
11Parts
4Variant Sets
10Variants
13Annotons
9Connections

Derived QC

Recommended-field compliance

81.8% recommended fields populated
  • references[0] · findings (0/1)
  • references[1] · findings (0/1)

Module deep research

✓ present

  • nad_biosynthesis_salvage-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

1 leaf node(s) with no concrete protein grounding:

Template conformance

every declared conforms_to bundle matches its template motif.

Gene-review completeness (10/18 grounded genes reviewed)

10 complete review(s) · 7 with deep research · 8 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
nadA Q88NH8
nadB Q88MZ2
nadC Q88PR1
nadD Q88DL5
nadE Q88DF6
NADSYN1 Q6IA69
NAMPT P43490
NMNAT1 Q9HAN9
Escherichia coli PncC P0A6G3
Escherichia coli NadD P0A752
Escherichia coli NadB P10902
Escherichia coli NadA P11458
Escherichia coli PncB P18133
Escherichia coli NadE P18843
Escherichia coli PncA P21369
Escherichia coli NadC P30011
pncB Q88DF7
pncC Q88ME5

Details

L-aspartate de novo and selected salvage routes to NAD+Metabolic Pathwaynad_biosynthesis_salvage
NAD+ biosynthetic processGO:0009435
Variant set: Complete NAD+ route realization by precursor deamidation state and completion chemistry (One Or More)

At least one complete route class must be selected. Neither class contains an empty or optional completion path.

NaMN-producing routes with deamido-NAD completionMetabolic Pathwaynamn_to_nad_realization

A complete realization selects one or more NaMN-producing alternatives and must then convert NaMN through deamido-NAD to NAD+.

Connections

The L-aspartate de novo route supplies NaMN to shared completion.
Direct nicotinate phosphoribosylation supplies NaMN to shared completion.
PncA followed by PncB supplies NaMN to shared completion.
PncC deamidation supplies NaMN to shared completion.
Part 1: produce NaMN by de novo synthesis or deamidated salvage
NaMN-producing precursor alternativesMetabolic Pathwaynamn_precursor_supply

Each alternative in this node ends in nicotinate D-ribonucleotide (NaMN). The selected alternative must therefore continue through NaMN adenylylation and deamido-NAD amidation rather than through direct NMN completion.

NAD+ biosynthetic processGO:0009435
Variant set: NaMN-producing route by source precursor and deamidation sequence (One Or More)
De novo NaMN synthesis from L-aspartateMetabolic Pathwayde_novo_aspartate_to_namn

The conserved bacterial route oxidizes L-aspartate to iminoaspartate, condenses that unstable intermediate with glycerone phosphate to form quinolinate, and phosphoribosylates quinolinate to NaMN.

'de novo' NAD+ biosynthetic process from L-aspartateGO:0034628

Connections

nadb_step -> nada_step Provides Input For
NadB supplies iminoaspartate to NadA.
nada_step -> nadc_step Provides Input For
NadA supplies quinolinate to NadC.
Part 1: L-aspartate oxidation
L-aspartate oxidase stepReactionnadb_step

Annotons

L-aspartate oxidase
nadb_activity
Participant: Family: L-aspartate oxidase family
Family:
L-aspartate oxidase familyPANTHER:PTHR42716
Representative Members: Escherichia coli NadBUniProtKB:P10902 Pseudomonas putida KT2440 NadBUniProtKB:Q88MZ2

Function

L-aspartate oxidase activityGO:0008734
Substrates: L-aspartateCHEBI:29991 dioxygenCHEBI:15379
Products: iminoaspartateCHEBI:77875 hydrogen peroxideCHEBI:16240

Processes

'de novo' NAD+ biosynthetic process from L-aspartateGO:0034628

Supplies iminoaspartate to quinolinate synthase.

Part 2: quinolinate formation
Quinolinate synthase stepReactionnada_step

Annotons

Quinolinate synthase A
nada_activity
Participant: Family: quinolinate synthase A family
Family:
quinolinate synthase A familyPANTHER:PTHR30573
Representative Members: Escherichia coli NadAUniProtKB:P11458 Pseudomonas putida KT2440 NadAUniProtKB:Q88NH8

Function

quinolinate synthetase A activityGO:0008987
Substrates: iminoaspartateCHEBI:77875 glycerone phosphateCHEBI:57642
Products: quinolinateCHEBI:29959 hydrogenphosphateCHEBI:43474 waterCHEBI:15377

Processes

quinolinate biosynthetic processGO:0019805

Produces quinolinate for phosphoribosylation.

Part 3: quinolinate phosphoribosylation to NaMN
Quinolinate phosphoribosyltransferase stepReactionnadc_step

Annotons

Nicotinate-nucleotide diphosphorylase (carboxylating)
nadc_activity
Participant: Family: quinolinate phosphoribosyltransferase family
Family:
quinolinate phosphoribosyltransferase familyPANTHER:PTHR32179
Representative Members: Escherichia coli NadCUniProtKB:P30011 Pseudomonas putida KT2440 NadCUniProtKB:Q88PR1

Function

nicotinate-nucleotide diphosphorylase (carboxylating) activityGO:0004514
Substrates: quinolinateCHEBI:29959 5-phospho-alpha-D-ribose 1-diphosphateCHEBI:58017
Products: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 carbon dioxideCHEBI:16526 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic processGO:0009435

Produces NaMN, the entry to shared completion.

Direct nicotinate Preiss-Handler entryMetabolic Pathwaynicotinate_preiss_handler_route

Annotons

Nicotinate phosphoribosyltransferase
pncb_direct_activity
Participant: Family: nicotinate phosphoribosyltransferase family
Family:
nicotinate phosphoribosyltransferase familyPANTHER:PTHR11098
Representative Members: Escherichia coli PncBUniProtKB:P18133 Pseudomonas putida KT2440 PncBUniProtKB:Q88DF7

Function

nicotinate phosphoribosyltransferase activityGO:0004516
Substrates: nicotinateCHEBI:32544 5-phospho-alpha-D-ribose 1-diphosphateCHEBI:58017 ATPCHEBI:30616 waterCHEBI:15377
Products: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 ADPCHEBI:456216 hydrogenphosphateCHEBI:43474 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Converts available nicotinate directly to NaMN.

Nicotinamide deamidation followed by Preiss-Handler entryMetabolic Pathwaynicotinamide_deamidating_route

Connections

pnca_step -> pncb_after_pnca_step Provides Input For
PncA supplies nicotinate to PncB.
Part 1: nicotinamide deamidation
Nicotinamidase stepReactionpnca_step

Annotons

Part 2: nicotinate phosphoribosylation
PncB step after PncAReactionpncb_after_pnca_step

Annotons

Nicotinate phosphoribosyltransferase
pncb_after_pnca_activity
Participant: Family: nicotinate phosphoribosyltransferase family
Family:
nicotinate phosphoribosyltransferase familyPANTHER:PTHR11098
Representative Members: Escherichia coli PncBUniProtKB:P18133 Pseudomonas putida KT2440 PncBUniProtKB:Q88DF7

Function

nicotinate phosphoribosyltransferase activityGO:0004516
Substrates: nicotinateCHEBI:32544 5-phospho-alpha-D-ribose 1-diphosphateCHEBI:58017 ATPCHEBI:30616 waterCHEBI:15377
Products: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 ADPCHEBI:456216 hydrogenphosphateCHEBI:43474 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Converts PncA-derived nicotinate to NaMN.

NMN deamidation to NaMNMetabolic Pathwaynmn_deamidating_route

Annotons

Nicotinamide-nucleotide amidase PncC
pncc_activity
Participant: Family: PncC/CinA C-terminal NMN deamidase family
Family:
PncC/CinA C-terminal NMN deamidase family The compact bacterial PncC architecture represented by E. coli PncC carries the experimentally established NMN deamidase role; no PANTHER family identifier is asserted.
Representative Members: Escherichia coli PncCUniProtKB:P0A6G3 Pseudomonas putida KT2440 PncCUniProtKB:Q88ME5

Function

nicotinamide-nucleotide amidase activityGO:0019159
Substrates: nicotinamide mononucleotide (NMN)CHEBI:14649 waterCHEBI:15377
Products: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 ammoniumCHEBI:28938

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Routes NMN into the shared NaMN completion branch.

Part 2: complete NaMN through deamido-NAD to NAD+
Shared NaMN completion through deamido-NADMetabolic Pathwayshared_namn_completion

NaMN from de novo synthesis or deamidating salvage is adenylylated to deamido-NAD and then amidated to NAD+. Distinct families can perform the adenylylation, and NAD synthetases differ in their usable nitrogen donor.

NAD+ biosynthetic processGO:0009435

Connections

NaMN adenylylation supplies deamido-NAD to NAD synthetase.
Part 1: NaMN adenylylation to deamido-NAD
NaMN adenylylation alternativesReactionnamn_adenylylation
Variant set: NaMN adenylyltransferase family by enzyme family (One Or More)
Bacterial NadD-family NaMN adenylyltransferaseReactionbacterial_nadd_variant

Annotons

Nicotinate-nucleotide adenylyltransferase
nadd_activity
Participant: Family: bacterial NadD family
Family:
bacterial NadD familyPANTHER:PTHR39321
Representative Members: Escherichia coli NadDUniProtKB:P0A752 Pseudomonas putida KT2440 NadDUniProtKB:Q88DL5

Function

nicotinate-nucleotide adenylyltransferase activityGO:0004515
Substrates: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 ATPCHEBI:30616
Products: deamido-NADCHEBI:58437 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic processGO:0009435

Performs the bacterial NaMN adenylylation step.

Bifunctional NMNAT-family NaMN adenylylationReactionbifunctional_nmnat_namn_variant

Annotons

NMNAT nicotinate-nucleotide adenylyltransferase activity
nmnat_namn_activity
Participant: Family: eukaryotic NMN adenylyltransferase family
Family:
eukaryotic NMN adenylyltransferase familyPANTHER:PTHR12039
Representative Members: Human NMNAT1UniProtKB:Q9HAN9

Function

nicotinate-nucleotide adenylyltransferase activityGO:0004515
Substrates: nicotinate D-ribonucleotide (NaMN)CHEBI:57502 ATPCHEBI:30616
Products: deamido-NADCHEBI:58437 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic processGO:0009435

Provides the NaMN activity of bifunctional NMNAT enzymes.

Part 2: deamido-NAD amidation to NAD+
NAD synthetase nitrogen-donor alternativesReactiondeamido_nad_amidation
Variant set: NAD synthetase nitrogen donor by nitrogen donor and enzyme architecture (One Or More)
Ammonia-dependent NAD synthetaseReactionammonia_dependent_nade_variant

Annotons

Ammonia-dependent NAD+ synthase
ammonia_nade_activity
Participant: Family: ammonia-dependent NAD synthetase subfamily
Family:
ammonia-dependent NAD synthetase subfamilyPANTHER:PTHR23090:SF7 PTHR23090:SF7 separates the compact ammonia-dependent enzymes from family members carrying a glutaminase module.
Representative Members: Escherichia coli NadEUniProtKB:P18843 Pseudomonas putida KT2440 NadEUniProtKB:Q88DF6

Function

NAD+ synthase activityGO:0008795
Substrates: deamido-NADCHEBI:58437 ammoniumCHEBI:28938 ATPCHEBI:30616
Products: NAD+CHEBI:57540 adenosine 5'-monophosphateCHEBI:456215 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic processGO:0009435

Completes NAD+ synthesis using free ammonium.

Glutamine-dependent NAD synthetaseReactionglutamine_dependent_nadsyn_variant

Annotons

Glutamine-dependent NAD+ synthase
glutamine_nadsyn_activity
Participant: Ortholog Of: human glutamine-dependent NAD synthetase NADSYN1
Ortholog Of:
human glutamine-dependent NAD synthetase NADSYN1UniProtKB:Q6IA69 Q6IA69 is a reviewed, experimentally supported two-domain enzyme with glutaminase and NAD synthetase activities. PTHR23090:SF9 is not used as the selector because the local family export also contains compact ammonia-dependent proteins.

Function

NAD+ synthase (glutamine-hydrolyzing) activityGO:0003952
Substrates: deamido-NADCHEBI:58437 L-glutamineCHEBI:58359 ATPCHEBI:30616 waterCHEBI:15377
Products: NAD+CHEBI:57540 L-glutamateCHEBI:29985 adenosine 5'-monophosphateCHEBI:456215 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic processGO:0009435

Completes NAD+ synthesis using glutamine-derived nitrogen.

NAMPT-produced NMN with direct NAD+ completionMetabolic Pathwaynmn_to_nad_realization

A complete amidated salvage realization preserves the nicotinamide amide in NMN and requires direct NMN adenylylation to NAD+.

Connections

NAMPT supplies NMN specifically to direct NMN adenylylation.
Part 1: produce NMN from nicotinamide
Nicotinamide phosphoribosylation to NMNMetabolic Pathwayamidated_nicotinamide_salvage_route

Annotons

Nicotinamide phosphoribosyltransferase
nampt_activity
Participant: Family: nicotinamide phosphoribosyltransferase family
Family:
nicotinamide phosphoribosyltransferase familyPANTHER:PTHR43816
Representative Members: Human NAMPTUniProtKB:P43490

Function

nicotinamide phosphoribosyltransferase activityGO:0047280
Substrates: nicotinamideCHEBI:17154 5-phospho-alpha-D-ribose 1-diphosphateCHEBI:58017
Products: nicotinamide mononucleotide (NMN)CHEBI:14649 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Preserves the amide while producing NMN for direct completion.

Part 2: adenylylate NMN directly to NAD+
Direct amidated NMN completionReactiondirect_nmn_completion

NMN adenylyltransferase preserves the carboxamide and converts NMN directly to NAD+, bypassing deamido-NAD and NAD synthetase.

Annotons

Nicotinamide-nucleotide adenylyltransferase
nmnat_nmn_activity
Participant: Family: eukaryotic NMN adenylyltransferase family
Family:
eukaryotic NMN adenylyltransferase familyPANTHER:PTHR12039
Representative Members: Human NMNAT1UniProtKB:Q9HAN9

Function

nicotinamide-nucleotide adenylyltransferase activityGO:0000309
Substrates: nicotinamide mononucleotide (NMN)CHEBI:14649 ATPCHEBI:30616
Products: NAD+CHEBI:57540 diphosphateCHEBI:33019

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Completes amidated NMN salvage without a separate amidation step.