Nicotine biosynthesis module (Nicotiana / Solanaceae)

A plant-scoped, recursively decomposable decomposition of nicotine biosynthesis as it operates in Nicotiana (tobacco / wild tobacco). Nicotine is an alkaloid built by condensing two separately made rings: a PYRIDINE ring supplied by the aspartate-derived NAD/quinolinate (pyridine nucleotide) branch, and a PYRROLIDINE ring (the N-methyl-Delta1-pyrrolinium cation) supplied by the polyamine/ornithine branch. The module separates these two upstream supply branches from the late "nicotine synthase" cascade that joins the rings, and from the vacuolar transport/metabolon step. This module is intentionally NOT a flat gene list (that lives in the per-gene NICAT reviews and the NICOTINE_BIOSYNTHESIS project). Its purpose is to capture the pathway-level structure that the individual gene reviews cannot: the two-branch convergence, the recently revised late steps, and the co-clustered transport component. The late steps are phrased to reflect the 2025-2026 revision of the pathway. In the classical model the N-methylpyrrolinium cation condensed with a nicotinic acid derivative directly. The new model ("complete biosynthesis of nicotine", Cell 2026, PMID:41928514; "nicotine biosynthesis completed by cryptic activating glucosylation", Nat Commun 2026, PMID:42151135) routes nicotinic acid through a hidden N-glucosylation/reduction/condensation/deglucosylation relay: a UDP-glucosyltransferase (UGT1/NaGT) glucosylates nicotinic acid to nicotinic acid N-glucoside, an A622/NaGR reductase and a BBL oxidase act on the activated glucoside during condensation with the pyrrolidine ring, and a beta-glucosidase (beta-GD1/NicGH) removes the sugar to release nicotine. A vacuolar-membrane MATE transporter (MATE1) co-clusters with A622 and beta-GD1 and is required for high heterologous production. This activating-glucosylation relay and the A622-MATE1-beta-GD1 metabolon are the parts of the pathway that GO biological-process and molecular-function terms flatten away.

MODULE:nicotine_biosynthesisDRAFTMetabolic Pathwaymodules/nicotine_biosynthesis.yaml
nicotine biosynthetic processGO:0042179
GO:0042179
nicotine biosynthetic process
The module is grounded in the GO biological-process term for nicotine biosynthesis.
file:projects/NICOTINE_BIOSYNTHESIS.md
Nicotine Biosynthesis Project
The per-gene NICAT review seed set, canonical pathway gene list, candidate accession mappings, and source bibliography that this module summarizes at the pathway level.
PMID:41928514
Complete biosynthesis of nicotine.
Reports the complete N. attenuata nicotine pathway, the new glycosylation (UGT1/NaGT) and deglycosylation (beta-GD1/NicGH) steps, the A622-MATE1-beta-GD1 cluster, and a minimal heterologous reconstruction set (NaODC, NaPMT1, NaMPO, NaUGT1, NaA622, NaBBL2, NaBGL1, NaMATE1).
PMID:42151135
Nicotine biosynthesis is completed by cryptic activating glucosylation.
Independent study (published version of the 2025 bioRxiv preprint) establishing the four-enzyme nicotine-synthase cascade (UGT1 -> A622 -> BBLa -> beta-GD1) in which a cryptic N-glucosylation activates nicotinic acid for condensation and is then removed.
file:genes/NICAT/NaPMT1.1/NaPMT1.1-ai-review.yaml
NaPMT1.1 NICAT review
Source of the verified putrescine N-methyltransferase grounding (GO:0030750) used in the pyrrolidine branch.

Grounding policy: GO molecular-function and biological-process identifiers were copied from the verified per-gene NICAT reviews (each harvested term is used in that gene's core_functions), so they are trusted. Metabolite/intermediate descriptors were grounded to ChEBI via EBI OLS exact-label lookup; descriptors that still lack a `term` (the N-methyl-Delta1-pyrrolinium cation, the nicotinic acid N-glucoside / reduced-glucoside intermediates, and small byproducts such as dioxygen / CO2 / ammonia / diphosphate where no unambiguous ChEBI exact match was returned) were left ungrounded rather than guessed. Representative UniProt members are the project's current sequence-backed NICAT candidate accessions (see the 2026-04-05 mapping dive in the project page); they are orienting exemplars, not official symbol normalizations and not a claim that the pathway is limited to those accessions. The NAMN-hydrolase step (NaNAMNH) and the ring-condensation step are real pathway steps for which no confident GO molecular-function id was available, so their function descriptors carry no term.

21Nodes
14Parts
3Variant Sets
6Variants
14Annotons
11Connections

Derived QC

Recommended-field compliance

20.0% recommended fields populated
  • references[0] · findings (0/1)
  • references[1] · findings (0/1)
  • references[2] · findings (0/1)
  • references[3] · findings (0/1)

Module deep research

✗ none found

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

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.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • ao_step → qpt_step [NOT_CHECKED]
  • a622_step → bbl_step [NOT_CHECKED]

Function consistency and core coverage

13 gene-function check(s) reflected in core functions · 0 conflict(s) · 7 evidence or coverage gap(s) (22 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
ao_activity NaAO2 candidate AO_0 (NICAT)
UniProtKB:A0A1J6KBX2
Family Representative 		L-aspartate oxidase activity
GO:0008734 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
qpt_activity NaQPT2 candidate QPT_0 (NICAT)
UniProtKB:A0A1J6KEF3
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).
namnh_activity ANY_WITH_FUNCTION
Gene 		nicotinic acid mononucleotide -> nicotinic acid (hydrolytic release)
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
namnh_activity:required_function ANY_WITH_FUNCTION
Gene 		nicotinate mononucleotide hydrolase / phosphatase-glycohydrolase activity
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
odc_activity NaODC candidate ODC (NICAT)
UniProtKB:A0A314KUM9
Family Representative 		ornithine decarboxylase activity
GO:0004586 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmt11_activity NaPMT1.1 (NICAT)
UniProtKB:Q93XQ5
Gene 		putrescine N-methyltransferase activity
GO:0030750 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pmt12_activity NaPMT1.2 (NICAT)
UniProtKB:Q93XQ4
Gene 		putrescine N-methyltransferase activity
GO:0030750 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mpo_activity NaMPO1 candidate AMO_3 (NICAT)
UniProtKB:A0A314KPU1
Family Representative 		N-methylputrescine oxidase activity
GO:0008131 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ugt_activity NaUGT1 candidate UGT85A2_0 (NICAT)
UniProtKB:A0A2H4GSI3
Family Representative 		UDP-glucosyltransferase activity (nicotinic acid N-glucosylation)
GO:0035251 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
a622_activity NaA622 (NICAT, via NCBI LOC109206509 / IFRH_2)
UniProtKB:A0A314KUK7
Family Representative 		nicotinic acid N-glucoside reductase / oxidoreductase activity
GO:0016491 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bbl2_activity NaBBL2 candidate FOX1_2 (NICAT)
UniProtKB:A0A1J6KPK0
Gene 		FAD-dependent (berberine-bridge-like) oxidoreductase activity
GO:0016491 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bbl1_activity NaBBL1 candidate FOX1_0 (NICAT)
UniProtKB:A0A1J6JGR6
Gene 		FAD-dependent (berberine-bridge-like) oxidoreductase activity
GO:0016491 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bgl1_activity NaBGL1 candidate BGLU18_6 (NICAT)
UniProtKB:A0A1J6KFZ7
Gene 		beta-glucosidase activity (nicotine glucoside hydrolysis)
GO:0008422 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bgl2_activity NaBGL2 candidate BGLU18_1 (NICAT)
UniProtKB:A0A314KWB2
Gene 		beta-glucosidase activity (nicotine glucoside hydrolysis)
GO:0008422 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mate1_activity NaMATE1 candidate DTX40_3 (NICAT)
UniProtKB:A0A314KVN4
Family Representative 		proton-coupled antiporter activity (alkaloid/intermediate transport)
GO:0015297 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ao_activity nicotine-pathway L-aspartate oxidase (NaAO2 / AO paralogs)
Family 		L-aspartate oxidase activity
GO:0008734 		Family Id Missing
The family has no identifier linking it to a curated family review.
qpt_activity nicotine-pathway QPT (NaQPT2 / QPT paralogs)
Family 		nicotinate-nucleotide diphosphorylase (carboxylating) activity
GO:0004514 		Family Id Missing
The family has no identifier linking it to a curated family review.
odc_activity nicotine-pathway ornithine decarboxylase (NaODC paralogs)
Family 		ornithine decarboxylase activity
GO:0004586 		Family Id Missing
The family has no identifier linking it to a curated family review.
mpo_activity N-methylputrescine oxidase (NaMPO1 / copper amine oxidase, AMO)
Family 		N-methylputrescine oxidase activity
GO:0008131 		Family Id Missing
The family has no identifier linking it to a curated family review.
ugt_activity nicotinic acid glucosyltransferase (NaUGT1 / NaGT, UGT85A2-like)
Family 		UDP-glucosyltransferase activity (nicotinic acid N-glucosylation)
GO:0035251 		Family Id Missing
The family has no identifier linking it to a curated family review.
a622_activity A622 / NaGR (isoflavone-reductase-like, PIP family)
Family 		nicotinic acid N-glucoside reductase / oxidoreductase activity
GO:0016491 		Family Id Missing
The family has no identifier linking it to a curated family review.
mate1_activity MATE1 / DTX40 (multidrug-and-toxic-compound-extrusion antiporter)
Family 		proton-coupled antiporter activity (alkaloid/intermediate transport)
GO:0015297 		Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (13/13 grounded genes reviewed)

11 complete review(s) · 13 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
NaA622 A0A314KUK7 ✓ ✓ ✓
NaAO2_candidate_AO_0 A0A1J6KBX2 ✓ ✓ ✓
NaBBL1_candidate_FOX1_0 A0A1J6JGR6 ✓ ✓ ✓
NaBBL2_candidate_FOX1_2 A0A1J6KPK0 ✓ ✓ ✓
NaBGL1_candidate_BGLU18_6 A0A1J6KFZ7 ✓ ✓ ✓
NaBGL2_candidate_BGLU18_1 A0A314KWB2 ✓ ✓ ✓
NaMATE1_candidate_DTX40_3 A0A314KVN4 ✓ 4/6 ✓
NaMPO1_candidate_AMO_3 A0A314KPU1 ✓ ✓ ✓
NaODC_candidate_ODC A0A314KUM9 ✓ ✓ ✓
NaQPT2_candidate_QPT_0 A0A1J6KEF3 ✓ ✓ ✓
NaUGT1_candidate_UGT85A2_0 A0A2H4GSI3 ✓ 3/6 ✓
PMT1 Q93XQ5 ✓ ✓ ✓
PMT2 Q93XQ4 ✓ ✓ ✓

Details

Context
Nicotiana (wild and cultivated tobacco)NCBITaxon:4085
rootPO:0009005
cytosol / vacuole metabolon
Nicotine biosynthesis (Nicotiana)Metabolic Pathwaynicotine_biosynthesis
nicotine biosynthetic processGO:0042179
Context
Nicotiana (wild and cultivated tobacco)NCBITaxon:4085
rootPO:0009005
cytosol / vacuole metabolon

Layering: catalytic steps ground to the GO molecular-function terms verified in the per-gene NICAT reviews (GO:0008734, GO:0004514, GO:0004586, GO:0030750, GO:0008131, GO:0035251, GO:0016491, GO:0008422, GO:0015297); the pathway grounds to GO:0042179, and metabolite intermediates to ChEBI. The information this module adds beyond per-gene GO annotation is the PATHWAY SHAPE: (1) two independently synthesized rings (pyridine via NAD/quinolinate, pyrrolidine via polyamines) that converge only at condensation; (2) the revised late steps in which a cryptic activating N-glucosylation (UGT1) is later removed (beta-GD1), with A622 and BBL acting on the glucoside in between - a relay no single GO term captures; and (3) the co-clustered MATE1 transport component of the A622-MATE1-beta-GD1 metabolon. The NaNAMNH hydrolysis and the ring-condensation chemistry are real steps left without GO molecular-function ids rather than guessing. Quinolinate synthase (NaQS) and the regulators (NaERF1-like, NaMYC2) and the transport follow-up NaNUP are deliberately out of this core module's scope, consistent with the project's seed boundaries.

Connections

pyridine_branch -> ugt_step Provides Input For
The pyridine branch delivers free nicotinic acid, the substrate that UGT1 glucosylates to begin the cascade.
pyrrolidine_branch -> a622_step Provides Input For
The pyrrolidine branch delivers the N-methyl-Delta1-pyrrolinium cation, the ring partner condensed with the activated nicotinic acid glucoside during the A622/BBL steps.
ao_step -> qpt_step Precedes
Aspartate oxidation feeds the early NAD/quinolinate pathway upstream of the QPT diversion point.
qpt_step -> namnh_step Provides Input For
QPT makes nicotinic acid mononucleotide, which NaNAMNH hydrolyzes to free nicotinic acid.
namnh_step -> ugt_step Provides Input For
Free nicotinic acid from the NaMN hydrolase is the entry substrate of the glucosylation relay.
odc_step -> pmt_step Provides Input For
Ornithine decarboxylase supplies putrescine, the substrate methylated by PMT.
pmt_step -> mpo_step Provides Input For
PMT makes N-methylputrescine, oxidatively cyclized by MPO to the pyrrolinium cation.
ugt_step -> a622_step Provides Input For
Nicotinic acid N-glucoside made by UGT1 is the substrate reduced by A622/NaGR.
a622_step -> bbl_step Precedes
A622 reduction and BBL oxidation act in series during the ring condensation.
bbl_step -> bgd_step Provides Input For
The condensed, still-glucosylated nicotine intermediate is the substrate of the beta-glucosidase.
MATE1 is part of the same root-enriched, co-expressed A622-MATE1-beta-GD1 late metabolon as the deglucosylation step; required for high heterologous nicotine yield.
Part 1: pyridine ring supply (aspartate / NAD / quinolinate branch)
Pyridine ring branch (aspartate -> nicotinic acid)Metabolic Pathwaypyridine_branch

Supplies the pyridine ring of nicotine via the early NAD (de novo pyridine nucleotide) pathway from aspartate, diverted at nicotinic acid mononucleotide and hydrolyzed to free nicotinic acid for the late condensation. The duplicated, root-recruited copies (NaAO2, NaQPT2) are the nicotine-dedicated paralogs distinguished from the housekeeping NAD-pathway copies.

Part 1: aspartate entry into the pyridine branch
L-aspartate -> iminoaspartate (L-aspartate oxidase)Reactionao_step

Annotons

L-aspartate oxidase activity (NaAO2)
ao_activity
Participant: Family: nicotine-pathway L-aspartate oxidase (NaAO2 / AO paralogs)
Family:
nicotine-pathway L-aspartate oxidase (NaAO2 / AO paralogs) Root-recruited aspartate oxidase paralog of the de novo NAD pathway.
Representative Members: NaAO2 candidate AO_0 (NICAT)UniProtKB:A0A1J6KBX2

Function

L-aspartate oxidase activityGO:0008734
Substrates: L-aspartateCHEBI:29991 dioxygen
Products: iminoaspartate (2-iminobutanedioate)CHEBI:58831 hydrogen peroxideCHEBI:16240

Processes

NAD(+) biosynthetic process (pyridine ring supply)GO:0009435
Part 2: quinolinate -> nicotinic acid mononucleotide
Quinolinate -> nicotinic acid mononucleotide (quinolinate phosphoribosyltransferase)Reactionqpt_step

NaQPT2 is the root-specific, nicotine-dedicated quinolinate phosphoribosyltransferase paralog that channels quinolinate into nicotinic acid mononucleotide for the nicotine branch rather than only for housekeeping NAD synthesis.

Annotons

nicotinate-nucleotide diphosphorylase (carboxylating) activity (NaQPT2)
qpt_activity
Participant: Family: nicotine-pathway QPT (NaQPT2 / QPT paralogs)
Family:
nicotine-pathway QPT (NaQPT2 / QPT paralogs)
Representative Members: NaQPT2 candidate QPT_0 (NICAT)UniProtKB:A0A1J6KEF3

Function

nicotinate-nucleotide diphosphorylase (carboxylating) activityGO:0004514
Substrates: quinolinateCHEBI:16675 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)CHEBI:17111
Products: nicotinic acid mononucleotide (NaMN)CHEBI:15763 diphosphate carbon dioxide

Processes

NAD(+) biosynthetic processGO:0009435
Part 3: release of free nicotinic acid (new Cell 2026 step)
Nicotinic acid mononucleotide -> nicotinic acid (NaMN hydrolase, NaNAMNH)Reactionnamnh_step

The Cell 2026 paper assigns a NAMN hydrolase (NaNAMNH) that liberates free nicotinic acid as the pyridine-ring precursor fed into the late glucosylation relay. No confident GO molecular-function identifier is grounded here yet, and a stable public NICAT accession for NaNAMNH was still unresolved at module-authoring time.

Annotons

nicotinic acid mononucleotide hydrolase activity (NaNAMNH)
namnh_activity
Participant: Any With Function: nicotinate mononucleotide hydrolase / phosphatase-glycohydrolase activity
Required Function:
nicotinate mononucleotide hydrolase / phosphatase-glycohydrolase activity
Function is biochemically assigned by the Cell 2026 paper; participant accession not yet resolved in public NICAT annotation.

Function

nicotinic acid mononucleotide -> nicotinic acid (hydrolytic release)
Substrates: nicotinic acid mononucleotide (NaMN)CHEBI:15763
Products: nicotinic acidCHEBI:15940

Function descriptor intentionally carries no GO term: no confident grounding was available without guessing.

Part 2: pyrrolidine ring supply (ornithine / polyamine branch)
Pyrrolidine ring branch (ornithine -> N-methyl-Delta1-pyrrolinium cation)Metabolic Pathwaypyrrolidine_branch

Supplies the pyrrolidine ring as the N-methyl-Delta1-pyrrolinium cation via putrescine, N-methylputrescine, and 4-methylaminobutanal. PMT (putrescine N-methyltransferase) is the committed, root-specific entry that diverts polyamine metabolism toward alkaloids.

Part 1: putrescine supply
L-ornithine -> putrescine (ornithine decarboxylase)Reactionodc_step

Annotons

ornithine decarboxylase activity (NaODC1/NaODC2)
odc_activity
Participant: Family: nicotine-pathway ornithine decarboxylase (NaODC paralogs)
Family:
nicotine-pathway ornithine decarboxylase (NaODC paralogs)
Representative Members: NaODC candidate ODC (NICAT)UniProtKB:A0A314KUM9

Function

ornithine decarboxylase activityGO:0004586
Substrates: L-ornithineCHEBI:15729
Products: putrescineCHEBI:17148 carbon dioxide

Processes

putrescine biosynthetic process from arginine, via ornithineGO:0009446
Part 2: committed methylation step (pathway entry)
putrescine -> N-methylputrescine (putrescine N-methyltransferase)Reactionpmt_step

The committed, rate-influencing entry into the pyrrolidine alkaloid branch. Represented with isozyme variants because Nicotiana carries co-expressed PMT paralogs (NaPMT1.1, NaPMT1.2) that catalyze the same reaction.

Variant set: PMT paralogs by paralog / gene copy (One Or More)
NaPMT1.1Reactionpmt11_form

Annotons

putrescine N-methyltransferase activity (NaPMT1.1)
pmt11_activity
Participant: Gene Product: NaPMT1.1 (NICAT)
Gene Product:
NaPMT1.1 (NICAT)UniProtKB:Q93XQ5 Cell minimal-reconstruction PMT component; maps cleanly to UniProt PMT1.

Function

putrescine N-methyltransferase activityGO:0030750
Substrates: putrescineCHEBI:17148 S-adenosyl-L-methionineCHEBI:15414
Products: N-methylputrescineCHEBI:17166 S-adenosyl-L-homocysteineCHEBI:16680
NaPMT1.2Reactionpmt12_form

Annotons

putrescine N-methyltransferase activity (NaPMT1.2)
pmt12_activity
Participant: Gene Product: NaPMT1.2 (NICAT)
Gene Product:
NaPMT1.2 (NICAT)UniProtKB:Q93XQ4 Root-specific PMT paralog; maps cleanly to UniProt PMT2.

Function

putrescine N-methyltransferase activityGO:0030750
Substrates: putrescineCHEBI:17148 S-adenosyl-L-methionineCHEBI:15414
Products: N-methylputrescineCHEBI:17166 S-adenosyl-L-homocysteineCHEBI:16680
Part 3: oxidative cyclization to the pyrrolinium cation
N-methylputrescine -> N-methyl-Delta1-pyrrolinium cation (N-methylputrescine oxidase)Reactionmpo_step

Oxidative deamination of N-methylputrescine to 4-methylaminobutanal, which cyclizes spontaneously to the N-methyl-Delta1-pyrrolinium cation - the reactive pyrrolidine-ring donor for condensation.

Annotons

N-methylputrescine oxidase activity (NaMPO1)
mpo_activity
Participant: Family: N-methylputrescine oxidase (NaMPO1 / copper amine oxidase, AMO)
Family:
N-methylputrescine oxidase (NaMPO1 / copper amine oxidase, AMO)
Representative Members: NaMPO1 candidate AMO_3 (NICAT)UniProtKB:A0A314KPU1

Function

N-methylputrescine oxidase activityGO:0008131
Substrates: N-methylputrescineCHEBI:17166 dioxygen waterCHEBI:15377
Products: 4-methylaminobutanal (cyclizes to N-methyl-Delta1-pyrrolinium cation)CHEBI:1894 ammonia hydrogen peroxideCHEBI:16240

Grounded to GO:0008131 (primary methylamine oxidase activity), the verified term used in the NaMPO1 NICAT review; the physiological substrate is N-methylputrescine.

Part 3: ring condensation and activating-glucosylation relay (nicotine synthase)
Nicotine synthase cascade (cryptic activating glucosylation)Metabolic Pathwaynicotine_synthase_cascade

Joins the pyridine and pyrrolidine rings into nicotine. In the revised model nicotinic acid is first N-glucosylated to nicotinic acid N-glucoside (an activating, ultimately cryptic modification), the glucoside is reduced (A622/NaGR) and oxidized (BBL) during condensation with the N-methyl-Delta1-pyrrolinium cation, and a beta-glucosidase (beta-GD1/NicGH) finally removes the sugar to release nicotine.

Part 1: activating N-glucosylation of nicotinic acid
nicotinic acid -> nicotinic acid N-glucoside (UGT1 / NaGT)Reactionugt_step

Annotons

nicotinic acid N-glucosyltransferase activity (NaUGT1)
ugt_activity
Participant: Family: nicotinic acid glucosyltransferase (NaUGT1 / NaGT, UGT85A2-like)
Family:
nicotinic acid glucosyltransferase (NaUGT1 / NaGT, UGT85A2-like)
Representative Members: NaUGT1 candidate UGT85A2_0 (NICAT)UniProtKB:A0A2H4GSI3

Function

UDP-glucosyltransferase activity (nicotinic acid N-glucosylation)GO:0035251
Substrates: nicotinic acidCHEBI:15940 UDP-glucoseCHEBI:18066
Products: nicotinic acid N-glucoside (NG) UDPCHEBI:17659
Part 2: reduction of the activated glucoside during condensation
nicotinic acid N-glucoside reduction (A622 / NaGR)Reactiona622_step

A622, an isoflavone-reductase-like (PIP-family) enzyme, redefined in the new model as the nicotinic acid N-glucoside reductase (NaGR) acting in the condensation with the pyrrolidine ring.

Annotons

nicotinic acid N-glucoside reductase activity (NaA622)
a622_activity
Participant: Family: A622 / NaGR (isoflavone-reductase-like, PIP family)
Family:
A622 / NaGR (isoflavone-reductase-like, PIP family)
Representative Members: NaA622 (NICAT, via NCBI LOC109206509 / IFRH_2)UniProtKB:A0A314KUK7

Function

nicotinic acid N-glucoside reductase / oxidoreductase activityGO:0016491
Substrates: nicotinic acid N-glucoside (NG) NADPHCHEBI:16474
Products: reduced (dihydro) nicotinic acid N-glucoside intermediate
Part 3: late oxidation joining the rings
berberine-bridge-like oxidation (BBL / BBLa)Reactionbbl_step

FAD-dependent berberine-bridge-enzyme-like oxidase acting late in the condensation. Represented with paralog variants because Nicotiana carries multiple BBL copies (NaBBL1, NaBBL2), with NaBBL2 used in the Cell minimal yeast reconstruction.

Variant set: BBL paralogs by paralog / gene copy (One Or More)
NaBBL2 (FOX1_2, minimal-set component)Reactionbbl2_form

Annotons

BBL oxidase activity (NaBBL2)
bbl2_activity
Participant: Gene Product: NaBBL2 candidate FOX1_2 (NICAT)
Gene Product:
NaBBL2 candidate FOX1_2 (NICAT)UniProtKB:A0A1J6KPK0

Function

FAD-dependent (berberine-bridge-like) oxidoreductase activityGO:0016491
NaBBL1 (FOX1_0)Reactionbbl1_form

Annotons

BBL oxidase activity (NaBBL1)
bbl1_activity
Participant: Gene Product: NaBBL1 candidate FOX1_0 (NICAT)
Gene Product:
NaBBL1 candidate FOX1_0 (NICAT)UniProtKB:A0A1J6JGR6

Function

FAD-dependent (berberine-bridge-like) oxidoreductase activityGO:0016491
Part 4: deglucosylation releasing nicotine
glucoside hydrolysis to nicotine (beta-GD1 / NicGH, NaBGL1)Reactionbgd_step

The cryptic sugar added by UGT1 is removed by a beta-glucosidase (beta-GD1 / NicGH), releasing free nicotine. Represented with paralog variants (NaBGL1 / NaBGL2; BGLU18 family) per the project's sequence-backed mapping that favors BGLU18 over the older BGLU42 comparator.

Variant set: beta-GD paralogs by paralog / gene copy (One Or More)
NaBGL1 / beta-GD1 (BGLU18_6)Reactionbgl1_form

Annotons

beta-glucosidase activity (NaBGL1)
bgl1_activity
Participant: Gene Product: NaBGL1 candidate BGLU18_6 (NICAT)
Gene Product:
NaBGL1 candidate BGLU18_6 (NICAT)UniProtKB:A0A1J6KFZ7

Function

beta-glucosidase activity (nicotine glucoside hydrolysis)GO:0008422
Substrates: nicotine N-glucoside intermediate
Products: nicotineCHEBI:18723 D-glucoseCHEBI:17634
NaBGL2 / beta-GD2 (BGLU18_1)Reactionbgl2_form

Annotons

beta-glucosidase activity (NaBGL2)
bgl2_activity
Participant: Gene Product: NaBGL2 candidate BGLU18_1 (NICAT)
Gene Product:
NaBGL2 candidate BGLU18_1 (NICAT)UniProtKB:A0A314KWB2

Function

beta-glucosidase activity (nicotine glucoside hydrolysis)GO:0008422
Part 4: vacuolar transport / metabolon component (optional)
MATE1 vacuolar transport (A622-MATE1-beta-GD1 metabolon)Transport Steptransport_metabolon

A MATE/DTX-family proton-antiporter (MATE1) co-clusters and is tightly co-expressed with A622 and beta-GD1, and is required for high heterologous nicotine production. The exact transported metabolite (a glucosylated intermediate vs nicotine itself) is unresolved, so this is modelled as an optional transport component of the late metabolon rather than a defined catalytic step.

Annotons

MATE/antiporter transport activity (NaMATE1)
mate1_activity
Participant: Family: MATE1 / DTX40 (multidrug-and-toxic-compound-extrusion antiporter)
Family:
MATE1 / DTX40 (multidrug-and-toxic-compound-extrusion antiporter)
Representative Members: NaMATE1 candidate DTX40_3 (NICAT)UniProtKB:A0A314KVN4

Function

proton-coupled antiporter activity (alkaloid/intermediate transport)GO:0015297

Locations

vacuolar membrane / tonoplastGO:0005774

Transport/sequestration component of the late nicotine metabolon; specific transported species not yet defined.