Function
Forms the phosphorylated HMP pyrimidine moiety.
Species-neutral bacterial pathway for de novo synthesis of thiamine diphosphate (ThDP), the active thiamine cofactor. The pathway has two converging branches: a hydroxymethylpyrimidine branch in which ThiC converts an AIR-derived precursor to HMP phosphate and ThiD phosphorylates it to the diphosphate, and a thiazole branch in which Dxs, alternative ThiO or ThiH routes, sulfur-relay proteins, and ThiG form the thiazole phosphate moiety. ThiE couples the pyrimidine and thiazole moieties to thiamine phosphate, and ThiL phosphorylates thiamine phosphate to ThDP. The thiazole branch includes the ThiS sulfur-carrier activation/thiocarboxylation relay rather than treating sulfur delivery as a single enzyme reaction.
This module is narrower than KEGG ppu00730 "Thiamine metabolism": it models de novo ThDP biosynthesis. Adenylate kinase (adk), RsgA, thiamine triphosphatase, aminopyrimidine aminohydrolases, and transport/salvage proteins are pathway neighbors or salvage context rather than required core biosynthetic steps. In P. putida KT2440, PP_5105 encodes the ThiS sulfur carrier and is a likely module member even though it is assigned to KEGG sulfur-relay map ppu04122 rather than ppu00730. The KT2440 ThiF-type ThiS adenylylation enzyme is unresolved: OpenScientist found no dedicated thiF and nominated MoeB/PP_0735 as the only plausible but unconfirmed E1-like substitute, so the module keeps a species-neutral ThiF-family step and records the PSEPK assignment as a curation gap.
All recommended fields populated.
✓ present
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
4 gene-function check(s) reflected in core functions · 0 conflict(s) · 19 evidence or coverage gap(s) (23 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.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| phosphomethylpyrimidine_synthase_activity | thiC (Pseudomonas putida KT2440) UniProtKB:Q88DA5 Family Representative |
phosphomethylpyrimidine synthase activity GO:0070284 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| phosphomethylpyrimidine_kinase_activity | thiD (Pseudomonas putida KT2440) UniProtKB:Q88DP2 Family Representative |
phosphomethylpyrimidine kinase activity GO:0008972 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| dxp_synthase_activity | dxs (Pseudomonas putida KT2440) UniProtKB:Q88QG7 Family Representative |
1-deoxy-D-xylulose-5-phosphate synthase activity GO:0008661 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| glycine_oxidase_activity | thiO (Pseudomonas putida KT2440) UniProtKB:Q88Q83 Family Representative |
glycine oxidase activity GO:0043799 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| glycine_oxidase_activity | thiO (Bacillus subtilis 168) UniProtKB:O31616 Family Representative |
glycine oxidase activity GO:0043799 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| iminoacetate_synthase_activity | thiH (Escherichia coli K-12) UniProtKB:P30140 Family Representative |
2-iminoacetate synthase activity GO:0036355 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| cysteine_desulfurase_activity | iscS (Pseudomonas putida KT2440) UniProtKB:Q88PK8 Family Representative |
cysteine desulfurase activity GO:0031071 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| cysteine_desulfurase_activity | iscS-II (Pseudomonas putida KT2440) UniProtKB:Q88K56 Family Representative |
cysteine desulfurase activity GO:0031071 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| thiF_this_adenylylation_activity | thiF (Escherichia coli K-12) UniProtKB:P30138 Family Representative |
ThiS ubiquitin-like sulfur-carrier activating enzyme activity GO:0008641 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| thiS_sulfur_carrier_role | ThiS sulfur carrier protein (Pseudomonas putida KT2440) UniProtKB:Q88CS5 Gene |
sulfur carrier activity GO:0097163 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| thiazole_synthase_activity | thiG (Pseudomonas putida KT2440) UniProtKB:Q88CS6 Family Representative |
thiazole synthase activity GO:1990107 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| thiamine_phosphate_diphosphorylase_activity | thiE (Pseudomonas putida KT2440) UniProtKB:Q88DP1 Family Representative |
thiamine-phosphate diphosphorylase activity GO:0004789 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| thiamine_phosphate_kinase_activity | thiL (Pseudomonas putida KT2440) UniProtKB:Q88QH4 Family Representative |
thiamine-phosphate kinase activity GO:0009030 |
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. |
| phosphomethylpyrimidine_synthase_activity | ThiC phosphomethylpyrimidine synthase family PANTHER:PTHR30557 Family |
phosphomethylpyrimidine synthase activity GO:0070284 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR30557. |
| phosphomethylpyrimidine_kinase_activity | ThiD hydroxymethylpyrimidine/phosphomethylpyrimidine kinase family PANTHER:PTHR20858 Family |
phosphomethylpyrimidine kinase activity GO:0008972 |
Family Scope Restricted
GO:0008972 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. ThiD/THI20 subfamilies, as both thiamine modules assert on the base family. THI22 is a member exception. |
| dxp_synthase_activity | Dxs 1-deoxy-D-xylulose-5-phosphate synthase family PANTHER:PTHR43322 Family |
1-deoxy-D-xylulose-5-phosphate synthase activity GO:0008661 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR43322. |
| glycine_oxidase_activity | ThiO glycine oxidase family PANTHER:PTHR13847:SF289 Family |
glycine oxidase activity GO:0043799 |
Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0043799. |
| iminoacetate_synthase_activity | ThiH 2-iminoacetate synthase family PANTHER:PTHR43583:SF1 Family |
2-iminoacetate synthase activity GO:0036355 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR43583:SF1. |
| cysteine_desulfurase_activity | IscS cysteine desulfurase family PANTHER:PTHR11601 Family |
cysteine desulfurase activity GO:0031071 |
Family Scope Restricted
GO:0031071 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Cysteine desulfurase activity is experimentally established for SF34 members in bacteria (E. coli IscS) and eukaryotes (NFS1) and is the shared chemistry of the small bacterial SF36 and SF50 groups. It is excluded from the selenocysteine lyase subfamily SF62, which is specific for L-selenocysteine. |
| thiF_this_adenylylation_activity | ThiF sulfur carrier protein ThiS adenylyltransferase subfamily PANTHER:PTHR10953:SF240 Family |
ThiS ubiquitin-like sulfur-carrier activating enzyme activity GO:0008641 |
Family Function Unreviewed
Family review leaves GO:0008641 UNRESOLVED. GO defines this activity as activation of a ubiquitin-like protein through formation of an ATP-dependent high-energy thiolester bond. The eukaryotic E1 and ATG7 subfamilies meet that definition. The bacterial ThiF (SF240) and MoeB (SF194) enzymes adenylate their ubiquitin-fold carriers (ThiS, MoaD), but for MoeB no E1-like thioester intermediate was observed. Whether ThiF forms a thioester with ThiS was not adjudicated here, so the term is not granted to SF240 or SF194. |
| thiazole_synthase_activity | ThiG thiazole synthase family PANTHER:PTHR34266 Family |
thiazole synthase activity GO:1990107 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR34266. |
| thiamine_phosphate_diphosphorylase_activity | ThiE thiamine-phosphate synthase family PANTHER:PTHR20857 Family |
thiamine-phosphate diphosphorylase activity GO:0004789 |
Family Scope Restricted
GO:0004789 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. ThiE (SF15) and bifunctional THI6 (SF23). eukaryotic_thiamine_biosynthesis selects SF23; thiamine_diphosphate_biosynthesis selects the base family, which also takes in TenI. |
| thiamine_phosphate_kinase_activity | ThiL thiamine-phosphate kinase family PANTHER:PTHR30270 Family |
thiamine-phosphate kinase activity GO:0009030 |
Family Review Missing
No supported structured family review is available for PANTHER:PTHR30270. |
4 complete review(s) · 4 with deep research · 9 missing review · 1 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| dxs Q88QG7 | ✓ | ✓ | ✓ |
| iscS Q88PK8 | ✓ | 5/6 | ✓ |
| thiO (Bacillus subtilis 168) O31616 | ✗ | — | — |
| thiF (Escherichia coli K-12) P30138 | ✗ | — | — |
| ThiS sulfur carrier protein (Pseudomonas putida KT2440) Q88CS5 | ✗ | — | — |
| thiG (Pseudomonas putida KT2440) Q88CS6 | ✗ | — | — |
| thiC (Pseudomonas putida KT2440) Q88DA5 | ✗ | — | — |
| thiE (Pseudomonas putida KT2440) Q88DP1 | ✗ | — | — |
| thiD (Pseudomonas putida KT2440) Q88DP2 | ✗ | — | — |
| iscS-II (Pseudomonas putida KT2440) Q88K56 | ✗ | — | — |
| thiL (Pseudomonas putida KT2440) Q88QH4 | ✗ | — | — |
| thiH P30140 | ✓ | ✓ | ✗ |
| thiI Q88CY4 | ✓ | ✓ | ✓ |
| thiO Q88Q83 | ✓ | ✓ | ✓ |
Produces the activated pyrimidine moiety, HMP diphosphate, for coupling to thiazole phosphate.
Forms the phosphorylated HMP pyrimidine moiety.
Activates HMP phosphate to the diphosphate used by ThiE.
ThiD-family enzymes may also support HMP salvage via hydroxymethylpyrimidine kinase activity; this annoton represents the de novo HMP-P to HMP-PP step.
Produces the thiazole phosphate moiety from DXP, ThiO- or ThiH-derived 2-iminoacetate, and sulfur carried through IscS/ThiI/ThiS.
Supplies DXP, the carbon precursor for the thiazole moiety.
DXP is also used in non-mevalonate isoprenoid biosynthesis; the Dxs step is substrate supply for this module rather than a thiamine-specific commitment step.
Supplies the 2-iminoacetate (dehydroglycine) input to ThiG through oxygen-dependent ThiO or radical-SAM ThiH chemistry.
Supplies 2-iminoacetate from glycine under oxic conditions. PTHR13847:SF289 also contains proteins annotated with other functions, so the exact MF and reviewed exemplars constrain this role; no glycine-oxidase PAINT node is asserted.
Supplies 2-iminoacetate from tyrosine through oxygen-sensitive radical-SAM chemistry.
Mobilizes sulfur as persulfide for ThiI-mediated ThiS thiocarboxylation.
P. putida KT2440 encodes iscS and iscS-II candidates; the exact thiamine-branch contributor should be checked in full gene reviews.
Activates the ThiS C-terminus by ATP-dependent adenylylation before sulfur transfer and thiocarboxylate formation.
P. putida KT2440 lacks a dedicated thiF gene. MoeB/PP_0735 is an E1-like PTHR10953 paralog and the only plausible local substitute identified by OpenScientist, but it remains a candidate_uncertain member until full gene review or experiment resolves whether it activates ThiS in vivo.
Transfers sulfur to the ThiS sulfur carrier to form ThiS thiocarboxylate for thiazole biosynthesis.
GO currently lacks the precise ThiS sulfur-carrier protein sulfurtransferase MF proposed in the PSEPK thiI review, so this role is represented by the specific thiazole process and curator notes rather than a broad sulfurtransferase MF.
Carries activated sulfur for ThiG-mediated thiazole phosphate formation.
PP_5105 is assigned to KEGG sulfur-relay map ppu04122 in the local partition but is a likely missing ppu00730 member for the thiazole branch.
Forms the activated thiazole phosphate moiety.
Couples the pyrimidine and thiazole moieties to form thiamine phosphate.
Produces the active cofactor thiamine diphosphate.