Fungal NAD+ biosynthesis from tryptophan and pyridine salvage

NAD+ supply network of yeasts and other fungi, in which several precursor routes converge on nicotinate mononucleotide (NaMN) or nicotinamide mononucleotide (NMN) and then share the final adenylylation and amidation steps. De novo synthesis uses the kynurenine pathway: an indoleamine 2,3-dioxygenase-family enzyme opens L-tryptophan to N-formylkynurenine, a kynurenine formamidase releases kynurenine, kynurenine 3-monooxygenase and kynureninase give 3-hydroxyanthranilate, 3-hydroxyanthranilate 3,4-dioxygenase opens the ring to 2-amino-3-carboxymuconate semialdehyde, which cyclizes non-enzymatically to quinolinate, and quinolinate phosphoribosyltransferase makes NaMN. Fungi lack the aspartate-derived (NadA/NadB) de novo route. In the Preiss-Handler salvage route, nicotinamide released by NAD+-consuming enzymes is deamidated by a nicotinamidase and the resulting nicotinate is converted to NaMN by nicotinate phosphoribosyltransferase. Nicotinamide riboside and nicotinic acid riboside are either phosphorylated by nicotinamide riboside kinase (to NMN or NaMN) or cleaved to the free bases by nucleosidases and nucleoside phosphorylases, which then enter the Preiss-Handler route. NaMN is adenylylated to nicotinate adenine dinucleotide (NaAD) by NMN/NaMN adenylyltransferases and amidated to NAD+ by a glutamine-dependent NAD+ synthetase, whereas NMN is adenylylated directly to NAD+. The de novo route requires oxygen, so fermenting yeasts depend on salvage under anaerobic conditions. Precursor uptake, NAD+-consuming reactions such as sirtuin deacetylation, and NADP+ formation are outside the module.

MODULE:nad_de_novo_and_salvage_fungalDRAFTMetabolic Pathwaymodules/nad_de_novo_and_salvage_fungal.yaml
NAD+ biosynthetic processGO:0009435 'de novo' NAD+ biosynthetic process from L-tryptophanGO:0034354 NAD+ biosynthetic process via the salvage pathwayGO:0034355
GO:0009435
NAD+ biosynthetic process
Module-level process for the convergent NAD+ supply network.
GO:0034354
'de novo' NAD+ biosynthetic process from L-tryptophan
Grounds the kynurenine de novo route. GO:0034354 is obsolete in current GO (2026 releases), replaced by GO:0034628, which now carries 'from L-tryptophan' and 'kynurenine pathway' as synonyms although its definition text still describes only the L-aspartate route. The concept keeps GO:0034354 because the ontology version used for validation in this repository still has it live with this label; migrate when the pinned GO is updated.
GO:0034355
NAD+ biosynthetic process via the salvage pathway
Grounds the nicotinamide, nicotinate and riboside salvage routes.
YeastPathways:PWY3O-4158
superpathway of NAD biosynthesis (S. cerevisiae, SGD YeastPathways)
Superpathway with BNA1-BNA7, NMA1, NMA2, QNS1, PNC1, NPT1, NRK1, URH1, PNP1 and SIR2. BNA3 is not the kynurenine formamidase (PMID:18205391) and SIR2 is an NAD+ consumer; both are excluded. POF1 and MEU1 are missing.
YeastPathways:NADSYN-PWY
NAD de novo biosynthesis II (from tryptophan) (S. cerevisiae, SGD YeastPathways)
Kynurenine route from tryptophan to NAD+; folded into the de novo variant and shared final steps.
YeastPathways:TRYPTOPHAN-DEGRADATION-1
L-tryptophan degradation III (eukaryotic) (S. cerevisiae, SGD YeastPathways)
Same reaction set as NADSYN-PWY drawn as tryptophan catabolism; in yeast this catabolism is the de novo NAD+ route.
YeastPathways:PWY-5651
L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde (S. cerevisiae, SGD YeastPathways)
First five kynurenine-route reactions (BNA2, BNA7, BNA4, BNA5, BNA1).
YeastPathways:PWY-5653
NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde (S. cerevisiae, SGD YeastPathways)
Non-enzymatic quinolinate formation, BNA6, NMA1/NMA2 and QNS1.
YeastPathways:PWY3O-4106
NAD salvage pathway IV (from nicotinamide riboside) (S. cerevisiae, SGD YeastPathways)
NRK1 phosphorylation of nicotinamide riboside and NMN adenylylation by NMA1/NMA2.
YeastPathways:PWY3O-4107
NAD salvage pathway V (PNC V cycle) (S. cerevisiae, SGD YeastPathways)
PNC1, NPT1, NMA1/NMA2 and QNS1 salvage with the SIR2 NAD+-consuming step that releases nicotinamide; SIR2 is outside the module.
YeastPathways:PWY3O-96
nicotinamide riboside salvage pathway II (S. cerevisiae, SGD YeastPathways)
URH1 hydrolysis and PNP1 phosphorolysis of nicotinamide riboside.
YeastPathways:PWY3O-224
nicotinate riboside salvage pathway I (S. cerevisiae, SGD YeastPathways)
Single-reaction NRK1 phosphorylation of nicotinic acid riboside; folded into the riboside kinase variant.
YeastPathways:PWY3O-236
nicotinate riboside salvage pathway II (S. cerevisiae, SGD YeastPathways)
URH1 and PNP1 cleavage of nicotinic acid riboside; folded into the riboside cleavage variant.
PMID:12062417
Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae.
Identifies the kynurenine-pathway BNA genes, shows that loss of the kynurenine pathway is co-lethal with npt1 deletion, and shows that yeast is a nicotinic acid auxotroph under anaerobic conditions.
PMID:18205391
Identification of formyl kynurenine formamidase and kynurenine aminotransferase from Saccharomyces cerevisiae using crystallographic, bioinformatic and biochemical evidence.
BNA7 (YDR428C) is the kynurenine formamidase; Bna3 is a kynurenine aminotransferase.
PMID:11816029
Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1.
PNC1 encodes the yeast nicotinamidase.
PMID:11884393
Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels.
NPT1 encodes the salvage nicotinate phosphoribosyltransferase; Npt1 and Nma2 are concentrated in the nucleus.
PMID:15137942
Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans.
Nrk1 phosphorylates nicotinamide riboside in a Preiss-Handler-independent route to NAD+.
PMID:17482543
Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+.
Nicotinamide riboside is used through Nrk1 and through an Nrk1-independent Urh1/Pnp1/Meu1 pathway.
PMID:17914902
Nicotinamide riboside kinase structures reveal new pathways to NAD+.
Nicotinic acid riboside is used by Nrk1 and NAD+ synthetase, and by Urh1, Pnp1 and Preiss-Handler salvage.
PMID:12597897
Identification and characterization of a second NMN adenylyltransferase gene in Saccharomyces cerevisiae.
YGR010W (NMA2) encodes a second yeast NMN adenylyltransferase.
PMID:24759102
YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae.
Pof1 is an NMN-specific adenylyltransferase required for normal NAD+ levels and NR use.
PMID:12771147
Eukaryotic NAD+ synthetase Qns1 contains an essential, obligate intramolecular thiol glutamine amidotransferase domain related to nitrilase.
Qns1 is a glutamine-dependent NAD+ synthetase with an essential nitrilase-related glutaminase domain.
file:yeast/PNC1/PNC1-ai-review.yaml
S. cerevisiae PNC1 gene review
Core function GO:0008936 nicotinamidase activity in nicotinate nucleotide salvage.
file:modules/kynurenine_nad_de_novo.yaml
Human kynurenine pathway module
Human counterpart of the de novo route; uses the same GO activities for each step.
file:modules/nad_biosynthesis_salvage.yaml
L-aspartate de novo and selected salvage routes to NAD+
Bacterial-centered module with the aspartate de novo route that fungi lack.
19Nodes
12Parts
2Variant Sets
6Variants
16Annotons
12Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:nad_de_novo_and_salvage_fungal deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

27 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (45 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
bna2_ido_activity BNA2 (Saccharomyces cerevisiae)
UniProtKB:P47125
Family Representative 		indoleamine 2,3-dioxygenase activity
GO:0033754 		Non Core Supported
The review explicitly retains this function as non-core; promotion into core_functions is not implied.
bna7_formamidase_activity BNA7 (Saccharomyces cerevisiae)
UniProtKB:Q04066
Family Representative 		arylformamidase activity
GO:0004061 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bna4_kmo_activity BNA4 (Saccharomyces cerevisiae)
UniProtKB:P38169
Family Representative 		kynurenine 3-monooxygenase activity
GO:0004502 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bna5_kynureninase_activity BNA5 (Saccharomyces cerevisiae)
UniProtKB:Q05979
Family Representative 		kynureninase activity
GO:0030429 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bna1_haao_activity BNA1 (Saccharomyces cerevisiae)
UniProtKB:P47096
Family Representative 		3-hydroxyanthranilate 3,4-dioxygenase activity
GO:0000334 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bna6_qprt_activity BNA6 (Saccharomyces cerevisiae)
UniProtKB:P43619
Family Representative 		nicotinate-nucleotide diphosphorylase (carboxylating) activity
GO:0004514 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnc1_nicotinamidase_activity PNC1 (Saccharomyces cerevisiae)
UniProtKB:P53184
Family Representative 		nicotinamidase activity
GO:0008936 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnc1_nicotinamidase_activity pnc1 (Schizosaccharomyces pombe)
UniProtKB:Q9USS0
Family Representative 		nicotinamidase activity
GO:0008936 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
npt1_naprt_activity NPT1 (Saccharomyces cerevisiae)
UniProtKB:P39683
Family Representative 		nicotinate phosphoribosyltransferase activity
GO:0004516 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
npt1_naprt_activity npt1 (Schizosaccharomyces pombe)
UniProtKB:Q9UTK3
Family Representative 		nicotinate phosphoribosyltransferase activity
GO:0004516 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nrk1_nicotinamide_riboside_kinase_activity NRK1 (Saccharomyces cerevisiae)
UniProtKB:P53915
Family Representative 		ribosylnicotinamide kinase activity
GO:0050262 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nrk1_nicotinamide_riboside_kinase_activity nrk1 (Schizosaccharomyces pombe)
UniProtKB:Q9C0W1
Family Representative 		ribosylnicotinamide kinase activity
GO:0050262 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nrk1_nicotinate_riboside_kinase_activity NRK1 (Saccharomyces cerevisiae)
UniProtKB:P53915
Family Representative 		nicotinate riboside kinase activity
GO:0061769 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nrk1_nicotinate_riboside_kinase_activity nrk1 (Schizosaccharomyces pombe)
UniProtKB:Q9C0W1
Family Representative 		nicotinate riboside kinase activity
GO:0061769 		Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
urh1_riboside_hydrolase_activity URH1 (Saccharomyces cerevisiae)
UniProtKB:Q04179
Family Representative 		nicotinamide riboside hydrolase activity
GO:0070635 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
urh1_riboside_hydrolase_activity urh1 (Schizosaccharomyces pombe)
UniProtKB:Q9P6J4
Family Representative 		nicotinamide riboside hydrolase activity
GO:0070635 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
urh1_riboside_hydrolase_activity urh2 (Schizosaccharomyces pombe)
UniProtKB:Q10314
Family Representative 		nicotinamide riboside hydrolase activity
GO:0070635 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnp1_riboside_phosphorylase_activity PNP1 (Saccharomyces cerevisiae)
UniProtKB:Q05788
Family Representative 		purine-nucleoside phosphorylase activity
GO:0004731 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pnp1_riboside_phosphorylase_activity SPAC1805.16c (Schizosaccharomyces pombe)
UniProtKB:Q9UTG1
Family Representative 		purine-nucleoside phosphorylase activity
GO:0004731 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_namn_adenylyltransferase_activity NMA1 (Saccharomyces cerevisiae)
UniProtKB:Q06178
Family Representative 		nicotinate-nucleotide adenylyltransferase activity
GO:0004515 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_namn_adenylyltransferase_activity NMA2 (Saccharomyces cerevisiae)
UniProtKB:P53204
Family Representative 		nicotinate-nucleotide adenylyltransferase activity
GO:0004515 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_namn_adenylyltransferase_activity SPAC806.06c (Schizosaccharomyces pombe)
UniProtKB:Q9UT53
Family Representative 		nicotinate-nucleotide adenylyltransferase activity
GO:0004515 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
qns1_nad_synthetase_activity QNS1 (Saccharomyces cerevisiae)
UniProtKB:P38795
Family Representative 		NAD+ synthase (glutamine-hydrolyzing) activity
GO:0003952 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
qns1_nad_synthetase_activity qns1 (Schizosaccharomyces pombe)
UniProtKB:O74940
Family Representative 		NAD+ synthase (glutamine-hydrolyzing) activity
GO:0003952 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_nmn_adenylyltransferase_activity NMA1 (Saccharomyces cerevisiae)
UniProtKB:Q06178
Family Representative 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_nmn_adenylyltransferase_activity NMA2 (Saccharomyces cerevisiae)
UniProtKB:P53204
Family Representative 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nma_nmn_adenylyltransferase_activity SPAC806.06c (Schizosaccharomyces pombe)
UniProtKB:Q9UT53
Family Representative 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pof1_nmn_adenylyltransferase_activity POF1 (Saccharomyces cerevisiae)
UniProtKB:P25576
Family Representative 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pof1_nmn_adenylyltransferase_activity SPAC694.03 (Schizosaccharomyces pombe)
UniProtKB:Q9P7T7
Family Representative 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bna2_ido_activity indoleamine 2,3-dioxygenase family
PANTHER:PTHR28657
Family 		indoleamine 2,3-dioxygenase activity
GO:0033754 		Family Supported
Family review supports GO:0033754 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and kynurenine_nad_de_novo; accepted by IDO1 and kept as non-core by BNA2, whose core is the tryptophan-specific term.
bna7_formamidase_activity fungal alpha/beta-hydrolase kynurenine formamidases
Family 		arylformamidase activity
GO:0004061 		Family Id Missing
The family has no identifier linking it to a curated family review.
bna4_kmo_activity kynurenine 3-monooxygenase family
PANTHER:PTHR46028
Family 		kynurenine 3-monooxygenase activity
GO:0004502 		Family Supported
Family review supports GO:0004502 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and kynurenine_nad_de_novo; accepted by KMO and BNA4.
bna5_kynureninase_activity kynureninase family
PANTHER:PTHR14084
Family 		kynureninase activity
GO:0030429 		Family Supported
Family review supports GO:0030429 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and kynurenine_nad_de_novo; accepted by BNA5 and KYNU.
bna1_haao_activity 3-hydroxyanthranilate 3,4-dioxygenase family
PANTHER:PTHR15497
Family 		3-hydroxyanthranilate 3,4-dioxygenase activity
GO:0000334 		Family Supported
Family review supports GO:0000334 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and kynurenine_nad_de_novo; accepted by BNA1 and HAAO.
bna6_qprt_activity quinolinate phosphoribosyltransferase family
PANTHER:PTHR32179:SF3
Family 		nicotinate-nucleotide diphosphorylase (carboxylating) activity
GO:0004514 		Family Supported
Family review supports GO:0004514 for PANTHER:PTHR32179:SF3. SF3; three modules (nad_de_novo_and_salvage_fungal, nad_biosynthesis_salvage, kynurenine_nad_de_novo) select the base family, which also takes in ModD.
pnc1_nicotinamidase_activity pyrazinamidase/nicotinamidase family
PANTHER:PTHR11080
Family 		nicotinamidase activity
GO:0008936 		Family Supported
Family review supports GO:0008936 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and nad_biosynthesis_salvage; accepted by PNC1 and pnc1.
npt1_naprt_activity nicotinate phosphoribosyltransferase family
PANTHER:PTHR11098
Family 		nicotinate phosphoribosyltransferase activity
GO:0004516 		Family Supported
Family review supports GO:0004516 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and nad_biosynthesis_salvage; accepted by P. putida PncB, NPT1, SPAC1486.06 and NAPRT.
nrk1_nicotinamide_riboside_kinase_activity nicotinamide riboside kinases (uridine kinase family)
PANTHER:PTHR10285:SF158
Family 		ribosylnicotinamide kinase activity
GO:0050262 		Family Supported
Family review supports GO:0050262 for PANTHER:PTHR10285:SF158. NRK subfamilies only, as nad_de_novo_and_salvage_fungal and nadp_synthesis_and_nr_salvage assert. Both modules select the base family.
nrk1_nicotinate_riboside_kinase_activity nicotinamide riboside kinases (uridine kinase family)
PANTHER:PTHR10285:SF158
Family 		nicotinate riboside kinase activity
GO:0061769 		Family Supported
Family review supports GO:0061769 for PANTHER:PTHR10285:SF158. NRK subfamilies only; accepted by S. cerevisiae NRK1, S. pombe nrk1 and human NMRK1/2.
urh1_riboside_hydrolase_activity fungal Urh1-type nucleosidases
PANTHER:PTHR12304:SF4
Family 		nicotinamide riboside hydrolase activity
GO:0070635 		Family Supported
Family review supports GO:0070635 for PANTHER:PTHR12304:SF4. Nicotinamide riboside hydrolysis by the fungal SF4 enzymes, as nad_de_novo_and_salvage_fungal selects.
pnp1_riboside_phosphorylase_activity purine nucleoside phosphorylases
PANTHER:PTHR11904
Family 		purine-nucleoside phosphorylase activity
GO:0004731 		Family Supported
Family review supports GO:0004731 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal, purine_nucleotide_catabolism and purine_salvage_and_catabolism; accepted by PNP1, SPAC1805.16c and PNP.
nma_namn_adenylyltransferase_activity NMN/NaMN adenylyltransferase family
PANTHER:PTHR12039
Family 		nicotinate-nucleotide adenylyltransferase activity
GO:0004515 		Family Supported
Family review supports GO:0004515 FAMILY_WIDE. Accepted by every reviewed member.
qns1_nad_synthetase_activity glutamine-dependent NAD+ synthetase subfamily
PANTHER:PTHR23090:SF9
Family 		NAD+ synthase (glutamine-hydrolyzing) activity
GO:0003952 		Family Supported
Family review supports GO:0003952 for PANTHER:PTHR23090:SF9. Glutamine-dependent SF9, as nad_de_novo_and_salvage_fungal selects.
nma_nmn_adenylyltransferase_activity NMN/NaMN adenylyltransferase family
PANTHER:PTHR12039
Family 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Family Supported
Family review supports GO:0000309 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal and nad_biosynthesis_salvage; accepted by every reviewed member.
pof1_nmn_adenylyltransferase_activity Pof1-type NMN adenylyltransferases
PANTHER:PTHR31285
Family 		nicotinamide-nucleotide adenylyltransferase activity
GO:0000309 		Family Supported
Family review supports GO:0000309 FAMILY_WIDE. Asserted by nad_de_novo_and_salvage_fungal; accepted by POF1 and SPAC694.03.

Gene-review completeness (24/24 grounded genes reviewed)

24 complete review(s) · 15 with deep research · 0 missing review · 9 reviewed but lacking deep research

Gene Review Complete Deep research
BNA1 P47096 ✓ ✓ ✓
BNA2 P47125 ✓ ✓ ✓
BNA4 P38169 ✓ ✓ ✓
BNA5 Q05979 ✓ ✓ ✓
BNA6 P43619 ✓ ✓ ✓
BNA7 Q04066 ✓ ✓ ✓
NMA1 Q06178 ✓ ✓ ✓
NMA2 P53204 ✓ ✓ ✓
NPT1 P39683 ✓ ✓ ✓
NRK1 P53915 ✓ ✓ ✓
nrk1 Q9C0W1 ✓ ✓ ✗
PNC1 P53184 ✓ ✓ ✓
pnc1 Q9USS0 ✓ ✓ ✗
PNP1 Q05788 ✓ ✓ ✓
POF1 P25576 ✓ ✓ ✓
QNS1 P38795 ✓ ✓ ✓
SPAC1486.06 Q9UTK3 ✓ ✓ ✗
SPAC17G8.02 Q10314 ✓ ✓ ✗
SPAC1805.16c Q9UTG1 ✓ ✓ ✗
SPAC694.03 Q9P7T7 ✓ ✓ ✗
SPAC806.06c Q9UT53 ✓ ✓ ✗
SPBC1683.06c Q9P6J4 ✓ ✓ ✗
SPCC553.02 O74940 ✓ ✓ ✗
URH1 Q04179 ✓ ✓ ✓

Details

Fungal NAD+ de novo synthesis and salvageMetabolic Pathwaynad_de_novo_and_salvage_fungal
NAD+ biosynthetic processGO:0009435 'de novo' NAD+ biosynthetic process from L-tryptophanGO:0034354 NAD+ biosynthetic process via the salvage pathwayGO:0034355

NEW module for the YeastPathways NAD group (2026-10). Ten YeastCyc frames (PWY3O-4158, NADSYN-PWY, TRYPTOPHAN-DEGRADATION-1, PWY-5651, PWY-5653, PWY3O-4106, PWY3O-4107, PWY3O-96, PWY3O-224, PWY3O-236) describe one convergent network, so they are modeled as four precursor-route variants feeding shared NaMN adenylylation, NAD+ synthetase and NMN adenylylation steps. The human MODULE:kynurenine_nad_de_novo covers the same de novo chemistry with TDO2/IDO1 and an ACMSD branch, and MODULE:nadp_synthesis_and_nr_salvage covers human NR kinases; the aspartate de novo route of MODULE:nad_biosynthesis_salvage is absent from fungi. YeastCyc corrections: BNA3 is a kynurenine aminotransferase, not the formamidase (PMID:18205391), and is excluded; SIR2 is an NAD+ consumer that releases nicotinamide and is excluded; POF1 (NMN-specific adenylyltransferase, PMID:24759102) is added; MEU1 is noted but not modeled. Compartments: all YeastPathways and PomBase activities are placed in the cytosol; Npt1 and Nma2 are also nuclear (PMID:11884393) and UniProt places Bna4 in the mitochondrial outer membrane, so no module-level compartment is asserted. Precursor transporters (nicotinate and nicotinamide riboside permeases) and the NMN/IMP nucleotidases that regenerate nicotinamide riboside are outside the boundary. GO-CAM disagreements: YeastPathways types URH1 as uridine nucleosidase and PNP1 as purine-nucleoside phosphorylase for the riboside reactions, and assigns arylformamidase activity to BNA3; PomBase 698e557b00000821 types the S. pombe PNP (SPAC1805.16c) as a nicotinamide riboside hydrolase and includes transporters and a thiazole synthase outside this module. S. pombe has no kynurenine-route genes in the PomBase model and is represented only in the salvage variants.

Connections

Part 1: formation of NaMN or NMN from precursors
Formation of NaMN or NMN by de novo synthesis or salvageMetabolic Pathwaypyridine_mononucleotide_supply

Four routes supply pyridine mononucleotides. Organisms and conditions use one or more of them; the kynurenine route is absent from fission yeast and needs oxygen in budding yeast.

Variant set: Pyridine mononucleotide supply routes by precursor route (One Or More)
Kynurenine de novo route from L-tryptophanMetabolic Pathwaykynurenine_de_novo_route
'de novo' NAD+ biosynthetic process from L-tryptophanGO:0034354

Connections

Part 1: tryptophan ring opening
L-tryptophan to N-formylkynurenineReactiontryptophan_dioxygenase_step

Annotons

Bna2-type indoleamine 2,3-dioxygenase
bna2_ido_activity
Participant: Family: indoleamine 2,3-dioxygenase family
Family:
indoleamine 2,3-dioxygenase familyPANTHER:PTHR28657
Representative Members: BNA2 (Saccharomyces cerevisiae)UniProtKB:P47125

Function

indoleamine 2,3-dioxygenase activityGO:0033754
Substrates: L-tryptophan dioxygen
Products: N-formyl-L-kynurenine
Cofactors: heme

Fungal Bna2 belongs to the IDO family rather than to the TDO family used by animal liver.

Part 2: formamide hydrolysis
N-formylkynurenine to L-kynurenineReactionkynurenine_formamidase_step

Annotons

Bna7 kynurenine formamidase
bna7_formamidase_activity
Participant: Family: fungal alpha/beta-hydrolase kynurenine formamidases
Family:
fungal alpha/beta-hydrolase kynurenine formamidases Bna7 has no PANTHER family assignment in UniProt, so no PANTHER term is asserted.
Representative Members: BNA7 (Saccharomyces cerevisiae)UniProtKB:Q04066

Function

arylformamidase activityGO:0004061
Substrates: N-formyl-L-kynurenine water
Products: L-kynurenine formate

Bna3, listed by YeastCyc for this step, is a kynurenine aminotransferase that diverts kynurenine to kynurenic acid and is not part of the module.

Part 3: kynurenine hydroxylation
L-kynurenine to 3-hydroxy-L-kynurenineReactionkynurenine_monooxygenase_step

Annotons

Bna4 kynurenine 3-monooxygenase
bna4_kmo_activity
Participant: Family: kynurenine 3-monooxygenase family
Family:
kynurenine 3-monooxygenase familyPANTHER:PTHR46028
Representative Members: BNA4 (Saccharomyces cerevisiae)UniProtKB:P38169

Function

kynurenine 3-monooxygenase activityGO:0004502
Substrates: L-kynurenine NADPH dioxygen
Products: 3-hydroxy-L-kynurenine NADP+ water
Cofactors: FAD

Commits kynurenine to the NAD+ branch.

Part 4: kynureninase cleavage
3-Hydroxy-L-kynurenine to 3-hydroxyanthranilateReactionkynureninase_step

Annotons

Bna5 kynureninase
bna5_kynureninase_activity
Participant: Family: kynureninase family
Family:
kynureninase familyPANTHER:PTHR14084
Representative Members: BNA5 (Saccharomyces cerevisiae)UniProtKB:Q05979

Function

kynureninase activityGO:0030429
Substrates: 3-hydroxy-L-kynurenine water
Products: 3-hydroxyanthranilate L-alanine
Cofactors: pyridoxal 5'-phosphate

PLP-dependent side-chain cleavage.

Part 5: aromatic ring opening
3-Hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehydeReactionhydroxyanthranilate_dioxygenase_step

Annotons

Bna1 3-hydroxyanthranilate 3,4-dioxygenase
bna1_haao_activity
Participant: Family: 3-hydroxyanthranilate 3,4-dioxygenase family
Family:
3-hydroxyanthranilate 3,4-dioxygenase familyPANTHER:PTHR15497
Representative Members: BNA1 (Saccharomyces cerevisiae)UniProtKB:P47096

Function

3-hydroxyanthranilate 3,4-dioxygenase activityGO:0000334
Substrates: 3-hydroxyanthranilate dioxygen
Products: 2-amino-3-carboxymuconate 6-semialdehyde
Cofactors: Fe(2+)

Its product cyclizes non-enzymatically to quinolinate; no ACMS decarboxylase competes for it in budding yeast according to YeastCyc, which lists none.

Part 6: quinolinate phosphoribosylation
Quinolinate to NaMNReactionquinolinate_phosphoribosyltransferase_step

Annotons

Bna6 quinolinate phosphoribosyltransferase
bna6_qprt_activity
Participant: Family: quinolinate phosphoribosyltransferase family
Family:
quinolinate phosphoribosyltransferase family
Representative Members: BNA6 (Saccharomyces cerevisiae)UniProtKB:P43619

Function

nicotinate-nucleotide diphosphorylase (carboxylating) activityGO:0004514
Substrates: quinolinate 5-phospho-alpha-D-ribose 1-diphosphate
Products: nicotinate D-ribonucleotide (NaMN) carbon dioxide diphosphate

Last de novo step, forming NaMN.

Nicotinamide deamidation and Preiss-Handler salvageMetabolic Pathwaynicotinamide_preiss_handler_route

Nicotinamide released by NAD+-consuming enzymes is deamidated to nicotinate, which is also taken up from the medium, and nicotinate is phosphoribosylated to NaMN.

Connections

Part 1: nicotinamide deamidation
Nicotinamide to nicotinateReactionnicotinamidase_step

Annotons

Pnc1 nicotinamidase
pnc1_nicotinamidase_activity
Participant: Family: pyrazinamidase/nicotinamidase family
Family:
pyrazinamidase/nicotinamidase familyPANTHER:PTHR11080
Representative Members: PNC1 (Saccharomyces cerevisiae)UniProtKB:P53184 pnc1 (Schizosaccharomyces pombe)UniProtKB:Q9USS0

Function

nicotinamidase activityGO:0008936
Substrates: nicotinamide water
Products: nicotinate ammonia

Fungi lack nicotinamide phosphoribosyltransferase, so nicotinamide is recycled through nicotinate.

Part 2: nicotinate phosphoribosylation
Nicotinate to NaMNReactionnicotinate_phosphoribosyltransferase_step

Annotons

Npt1 nicotinate phosphoribosyltransferase
npt1_naprt_activity
Participant: Family: nicotinate phosphoribosyltransferase family
Family:
nicotinate phosphoribosyltransferase familyPANTHER:PTHR11098
Representative Members: NPT1 (Saccharomyces cerevisiae)UniProtKB:P39683 npt1 (Schizosaccharomyces pombe)UniProtKB:Q9UTK3

Function

nicotinate phosphoribosyltransferase activityGO:0004516
Substrates: nicotinate 5-phospho-alpha-D-ribose 1-diphosphate ATP
Products: nicotinate D-ribonucleotide (NaMN) ADP diphosphate phosphate

Preiss-Handler entry to NaMN.

Nicotinamide and nicotinic acid riboside phosphorylation (Nrk)Reactionriboside_kinase_route

Annotons

Nrk1 nicotinamide riboside kinase
nrk1_nicotinamide_riboside_kinase_activity
Participant: Family: nicotinamide riboside kinases (uridine kinase family)
Family:
nicotinamide riboside kinases (uridine kinase family)PANTHER:PTHR10285:SF158 PANTHER 19.0 places both fungal representatives, S. cerevisiae NRK1 (P53915) and S. pombe nrk1 (Q9C0W1), in PTHR10285:SF158, together with the Candida albicans ortholog; the subfamily name SD05789P2 is an uninformative Drosophila gene-model identifier (its fly member is CG12016), not a statement about activity. The vertebrate NMRK1 and NMRK2 subfamilies (SF126, SF143) hold no fungal member and are omitted from this fungal module.
Representative Members: NRK1 (Saccharomyces cerevisiae)UniProtKB:P53915 nrk1 (Schizosaccharomyces pombe)UniProtKB:Q9C0W1

Function

ribosylnicotinamide kinase activityGO:0050262
Substrates: nicotinamide riboside ATP
Products: nicotinamide D-ribonucleotide (NMN) ADP

Preiss-Handler-independent route to NMN.

Nrk1 nicotinic acid riboside kinase
nrk1_nicotinate_riboside_kinase_activity
Participant: Family: nicotinamide riboside kinases (uridine kinase family)
Family:
nicotinamide riboside kinases (uridine kinase family)PANTHER:PTHR10285:SF158 PANTHER 19.0 places both fungal representatives, S. cerevisiae NRK1 (P53915) and S. pombe nrk1 (Q9C0W1), in PTHR10285:SF158, together with the Candida albicans ortholog; the subfamily name SD05789P2 is an uninformative Drosophila gene-model identifier (its fly member is CG12016), not a statement about activity. The vertebrate NMRK1 and NMRK2 subfamilies (SF126, SF143) hold no fungal member and are omitted from this fungal module.
Representative Members: NRK1 (Saccharomyces cerevisiae)UniProtKB:P53915 nrk1 (Schizosaccharomyces pombe)UniProtKB:Q9C0W1

Function

nicotinate riboside kinase activityGO:0061769
Substrates: nicotinate D-riboside ATP
Products: nicotinate D-ribonucleotide (NaMN) ADP

Nrk route from nicotinic acid riboside to NaMN.

Riboside cleavage to nicotinamide and nicotinate (Urh1/Pnp1)Metabolic Pathwayriboside_cleavage_route

An Nrk-independent route in which nucleosidases and nucleoside phosphorylases cleave nicotinamide riboside and nicotinic acid riboside to nicotinamide or nicotinate, which then enter the Pnc1/Npt1 route. Meu1 (methylthioadenosine phosphorylase) also contributes genetically (PMID:17482543) but its direct activity on ribosides is not established, so it is not an annoton.

Annotons

Urh1-type nicotinamide riboside hydrolase
urh1_riboside_hydrolase_activity
Participant: Family: fungal Urh1-type nucleosidases
Family:
fungal Urh1-type nucleosidasesPANTHER:PTHR12304:SF4
Representative Members: URH1 (Saccharomyces cerevisiae)UniProtKB:Q04179 urh1 (Schizosaccharomyces pombe)UniProtKB:Q9P6J4 urh2 (Schizosaccharomyces pombe)UniProtKB:Q10314

Function

nicotinamide riboside hydrolase activityGO:0070635
Substrates: nicotinamide riboside water
Products: nicotinamide D-ribose

The same enzymes hydrolyse nicotinic acid riboside (GO:0070636; PMID:17914902).

Pnp1 nucleoside phosphorylase acting on nicotinamide riboside
pnp1_riboside_phosphorylase_activity
Participant: Family: purine nucleoside phosphorylases
Family:
purine nucleoside phosphorylasesPANTHER:PTHR11904
Representative Members: PNP1 (Saccharomyces cerevisiae)UniProtKB:Q05788 SPAC1805.16c (Schizosaccharomyces pombe)UniProtKB:Q9UTG1

Function

purine-nucleoside phosphorylase activityGO:0004731
Substrates: nicotinamide riboside phosphate
Products: nicotinamide alpha-D-ribose 1-phosphate

GO has no specific pyridine-riboside phosphorylase term, so the purine-nucleoside phosphorylase term is used with the pyridine riboside named as substrate.

Part 2: NaMN adenylylation
NaMN to nicotinate adenine dinucleotide (NaAD)Reactionnamn_adenylyltransferase_step

Annotons

Nma1/Nma2 NaMN adenylyltransferase
nma_namn_adenylyltransferase_activity
Participant: Family: NMN/NaMN adenylyltransferase family
Family:
NMN/NaMN adenylyltransferase familyPANTHER:PTHR12039
Representative Members: NMA1 (Saccharomyces cerevisiae)UniProtKB:Q06178 NMA2 (Saccharomyces cerevisiae)UniProtKB:P53204 SPAC806.06c (Schizosaccharomyces pombe)UniProtKB:Q9UT53

Function

nicotinate-nucleotide adenylyltransferase activityGO:0004515
Substrates: nicotinate D-ribonucleotide (NaMN) ATP
Products: deamido-NAD+ (NaAD) diphosphate

Shared step for every NaMN-producing route.

Part 3: NaAD amidation
NaAD to NAD+Reactionnad_synthetase_step

Annotons

Qns1 glutamine-dependent NAD+ synthetase
qns1_nad_synthetase_activity
Participant: Family: glutamine-dependent NAD+ synthetase subfamily
Family:
glutamine-dependent NAD+ synthetase subfamilyPANTHER:PTHR23090:SF9
Representative Members: QNS1 (Saccharomyces cerevisiae)UniProtKB:P38795 qns1 (Schizosaccharomyces pombe)UniProtKB:O74940

Function

NAD+ synthase (glutamine-hydrolyzing) activityGO:0003952
Substrates: deamido-NAD+ (NaAD) L-glutamine ATP water
Products: NAD+ L-glutamate AMP diphosphate

Fused nitrilase-type glutaminase and synthetase; final step from NaMN-derived precursors.

Part 4: NMN adenylylation (riboside kinase branch) (optional)
NMN to NAD+Reactionnmn_adenylyltransferase_step

NMN made by Nrk1 is adenylylated directly to NAD+ by the dual-specificity Nma1/Nma2 enzymes or by the NMN-specific Pof1.

Variant set: NMN adenylyltransferase families by enzyme family (One Or More)
Dual-specificity Nma1/Nma2-type NMNATReactionnma_nmn_adenylyltransferase_variant

Annotons

Nma1/Nma2 NMN adenylyltransferase
nma_nmn_adenylyltransferase_activity
Participant: Family: NMN/NaMN adenylyltransferase family
Family:
NMN/NaMN adenylyltransferase familyPANTHER:PTHR12039
Representative Members: NMA1 (Saccharomyces cerevisiae)UniProtKB:Q06178 NMA2 (Saccharomyces cerevisiae)UniProtKB:P53204 SPAC806.06c (Schizosaccharomyces pombe)UniProtKB:Q9UT53

Function

nicotinamide-nucleotide adenylyltransferase activityGO:0000309
Substrates: nicotinamide D-ribonucleotide (NMN) ATP
Products: NAD+ diphosphate

The same proteins also adenylylate NaMN (step 2).

NMN-specific Pof1-type NMNATReactionpof1_nmn_adenylyltransferase_variant

Annotons

Pof1 NMN-specific adenylyltransferase
pof1_nmn_adenylyltransferase_activity
Participant: Family: Pof1-type NMN adenylyltransferases
Family:
Pof1-type NMN adenylyltransferasesPANTHER:PTHR31285
Representative Members: POF1 (Saccharomyces cerevisiae)UniProtKB:P25576 SPAC694.03 (Schizosaccharomyces pombe)UniProtKB:Q9P7T7

Function

nicotinamide-nucleotide adenylyltransferase activityGO:0000309
Substrates: nicotinamide D-ribonucleotide (NMN) ATP
Products: NAD+ diphosphate

Processes

NAD+ biosynthetic process via the salvage pathwayGO:0034355

Locations

cytoplasmGO:0005737 nucleusGO:0005634

Not listed by YeastCyc; required for normal NAD+ levels and efficient nicotinamide riboside use (PMID:24759102).