L-tryptophan biosynthesis (microbial)

De novo biosynthesis of L-tryptophan from chorismate, the branch-point precursor of the aromatic amino acids. Five enzymatic activities convert chorismate to L-tryptophan, drawing in L-glutamine (amide nitrogen), PRPP (5-phospho-alpha-D-ribose 1-diphosphate), and L-serine, and releasing pyruvate, CO2 and glyceraldehyde 3-phosphate along the way. The pathway is the classic textbook microbial operon (the trp operon) and is notable for extensive enzyme fusion and channeling: anthranilate synthase is a glutamine amidotransferase built from a synthase component (TrpE) and a glutaminase component (TrpD/TrpG), the latter frequently fused to anthranilate phosphoribosyltransferase in enteric bacteria; phosphoribosylanthranilate isomerase (TrpF) is often fused to indole-3-glycerol-phosphate synthase (TrpC); and the terminal tryptophan synthase is an alpha-2-beta-2 complex in which indole produced at the TrpA (alpha) active site is channeled through an intramolecular tunnel to the TrpB (beta) active site, where it condenses with L-serine, so free indole is not released. The pathway is feedback-regulated by L-tryptophan, classically at anthranilate synthase and, in many bacteria, also transcriptionally via attenuation and the TrpR repressor.

MODULE:tryptophan_biosynthesisDRAFTMetabolic Pathwaymodules/tryptophan_biosynthesis.yaml
L-tryptophan biosynthetic processGO:0000162
GapMind:aa
GapMind for amino acid biosynthesis
Step set and characterized-protein groundings derive from the GapMind amino-acid biosynthesis pathway definition trp.steps (PaperBLAST, Price & Arkin, LBL).
MetaCyc:TRPSYN-PWY
L-tryptophan biosynthesis
GapMind bases the tryptophan pathway on the MetaCyc pathway TRPSYN-PWY.
GO:0000162
L-tryptophan biosynthetic process
The module is grounded in the GO biological-process term for tryptophan biosynthesis.
8Nodes
5Parts
1Variant Sets
2Variants
8Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

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

Leaf nodes lacking representative members

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

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (0/0 grounded genes reviewed)

No concrete UniProt-grounded genes in this module.

Details

Context
cytosolGO:0005829
L-tryptophan biosynthesisMetabolic Pathwaytryptophan_biosynthesis
L-tryptophan biosynthetic processGO:0000162
Context
cytosolGO:0005829

Backbone and characterized-protein groundings were mined from GapMind trp.steps and ModelSEED (see modules/experimental/gapmind-mining/), then curated: GO molecular-function terms were verified via QuickGO, reaction chemistry and channeling/fusion notes were added, and the GapMind anthranilate-synthase OR-rule (two-component vs single-protein) was curated into an EXACTLY_ONE variant set. EC numbers that GapMind records only as ignore_other (the true reaction ECs 4.1.3.27, 4.1.2.8, 4.2.1.20) were reinstated as reaction evidence. Bifunctional microbial fusions are flagged: TrpD (trpD_1 + trpD_2), TrpC (PRAI + IGPS), and PriA (HisA + TrpF).

Connections

anthranilate_synthase_node -> trpD2_step Provides Input For
Anthranilate feeds the phosphoribosyltransferase step.
trpD2_step -> prai_step Precedes
prai_step -> igps_step Precedes
Part 1: chorismate to anthranilate (anthranilate synthase)
Chorismate to anthranilate (anthranilate synthase, alternative architectures)Reactionanthranilate_synthase_node

Anthranilate synthase aminates chorismate using the amide nitrogen of L-glutamine, eliminating pyruvate. It is a glutamine amidotransferase whose subunit architecture varies between taxa.

anthranilate synthase reaction
Variant set: Anthranilate synthase subunit architecture by enzyme architecture (Exactly One)
Two-component anthranilate synthase (TrpE + TrpD/TrpG)Protein Complextwo_component_anthranilate_synthase

The canonical (e.g. E. coli) arrangement: a synthase component (TrpE) plus a separate glutamine-amidotransferase component (TrpG, here trpD_1; in E. coli this is the N-terminal domain of the bifunctional TrpD protein).

Annotons

trpE: anthranilate synthase component I (synthase subunit)
trpE_activity
Participant: Family: anthranilate synthase component I (TrpE)
Family:
anthranilate synthase component I (TrpE)NCBIfam:TIGR00565
Required Function:
anthranilate synthase activityGO:0004049

Function

anthranilate synthase activityGO:0004049
Substrates: chorismate ammonia (channeled from the glutaminase subunit)
Products: anthranilate pyruvate

Synthase (component I) subunit; aminates chorismate and eliminates pyruvate.

trpD_1/trpG: glutamine amidotransferase component of anthranilate synthase
trpD1_activity
Participant: Family: anthranilate synthase glutamine amidotransferase component (TrpG/TrpD)
Family:
anthranilate synthase glutamine amidotransferase component (TrpG/TrpD)NCBIfam:TIGR00566
Required Function:
anthranilate synthase activityGO:0004049

Function

anthranilate synthase activityGO:0004049
Cofactors: L-glutamine (ammonia donor)

Glutaminase (component II) subunit; hydrolyses L-glutamine and channels ammonia to the TrpE active site. In E. coli this is the N-terminal domain of bifunctional TrpD, fused to anthranilate phosphoribosyltransferase.

Single-protein anthranilate synthase (TrpED, alphaproteobacterial clade)Reactionsingle_protein_anthranilate_synthase

Annotons

trpED: single-protein anthranilate synthase
trpED_activity
Participant: Family: single-protein anthranilate synthase (TrpED clade)
Family:
single-protein anthranilate synthase (TrpED clade)NCBIfam:TIGR01815
Required Function:
anthranilate synthase activityGO:0004049

Function

anthranilate synthase activityGO:0004049
Substrates: chorismate L-glutamine
Products: anthranilate pyruvate L-glutamate

Some alphaproteobacteria carry anthranilate synthase as a single fused polypeptide.

Part 2: anthranilate phosphoribosyltransferase (TrpD2)
Anthranilate to N-(5'-phosphoribosyl)-anthranilateReactiontrpD2_step

Annotons

trpD_2: anthranilate phosphoribosyltransferase
trpD2_activity
Participant: Any With Function: anthranilate phosphoribosyltransferase activity
Required Function:
anthranilate phosphoribosyltransferase activityGO:0004048

Function

anthranilate phosphoribosyltransferase activityGO:0004048
Substrates: anthranilate 5-phospho-alpha-D-ribose 1-diphosphate (PRPP)
Products: N-(5'-phospho-D-ribosyl)-anthranilate (PRA) diphosphate

In enteric bacteria such as E. coli this activity is the C-terminal domain of bifunctional TrpD, fused to the anthranilate synthase glutaminase component (trpD_1).

Part 3: phosphoribosylanthranilate isomerase (TrpF)
PRA to CdRPReactionprai_step

Annotons

PRAI/trpF: phosphoribosylanthranilate isomerase
prai_activity
Participant: Any With Function: phosphoribosylanthranilate isomerase activity
Required Function:
phosphoribosylanthranilate isomerase activityGO:0004640

Function

phosphoribosylanthranilate isomerase activityGO:0004640
Substrates: N-(5'-phospho-D-ribosyl)-anthranilate (PRA)
Products: 1-(o-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate (CdRP)

TrpF. Frequently fused to indole-3-glycerol-phosphate synthase as bifunctional TrpC. In some actinobacteria a single bifunctional PriA enzyme performs both this reaction (EC 5.3.1.24) and the analogous HisA reaction (EC 5.3.1.16) in histidine biosynthesis.

Part 4: indole-3-glycerol-phosphate synthase (TrpC)
CdRP to indole-3-glycerol phosphateReactionigps_step

Annotons

IGPS/trpC: indole-3-glycerol-phosphate synthase
igps_activity
Participant: Any With Function: indole-3-glycerol-phosphate synthase activity
Required Function:
indole-3-glycerol-phosphate synthase activityGO:0004425

Function

indole-3-glycerol-phosphate synthase activityGO:0004425
Substrates: 1-(o-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate (CdRP)
Products: (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate (indole-3-glycerol phosphate) carbon dioxide water

TrpC. Ring closure with decarboxylation; often fused to PRAI (TrpF).

Part 5: tryptophan synthase complex (TrpA + TrpB, channeled)
Indole-3-glycerol phosphate + L-serine to L-tryptophanReactiontryptophan_synthase_step

Tryptophan synthase is an alpha-2-beta-2 complex. The TrpA (alpha) active site retro-aldol-cleaves indole-3-glycerol phosphate to indole and glyceraldehyde 3-phosphate; the indole is channeled ~25 angstroms through an intramolecular tunnel to the PLP-dependent TrpB (beta) active site, where it condenses with L-serine to give L-tryptophan. Free indole is not released into the cytoplasm under normal operation.

Annotons

trpA: tryptophan synthase alpha subunit (indole-3-glycerol-phosphate lyase)
trpA_activity
Participant: Family: tryptophan synthase alpha chain (TrpA)
Family:
tryptophan synthase alpha chain (TrpA)NCBIfam:TIGR00262
Required Function:
tryptophan synthase activityGO:0004834

Function

tryptophan synthase activityGO:0004834
Substrates: (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate (indole-3-glycerol phosphate)
Products: indole (channeled to the beta subunit) D-glyceraldehyde 3-phosphate

Alpha subunit; cleaves indole-3-glycerol phosphate, feeding indole into the tunnel.

trpB: tryptophan synthase beta subunit
trpB_activity
Participant: Family: tryptophan synthase beta chain (TrpB)
Family:
tryptophan synthase beta chain (TrpB)NCBIfam:TIGR00263
Required Function:
tryptophan synthase activityGO:0004834

Function

tryptophan synthase activityGO:0004834
Substrates: indole (channeled from the alpha subunit) L-serine
Products: L-tryptophan water
Cofactors: pyridoxal 5'-phosphate

Beta subunit; PLP-dependent condensation of indole with L-serine to form L-tryptophan. Standalone "TrpB2" indole-salvage enzymes belong to a related family and may use phosphoserine.