dTDP-L-rhamnose biosynthesis

Species-neutral bacterial module for synthesis of the activated sugar dTDP-L-rhamnose from alpha-D-glucose 1-phosphate. The pathway proceeds through dTDP-glucose formation, dTDP-glucose 4,6-dehydration, dTDP-4-dehydrorhamnose 3,5-epimerization, and final NADPH-dependent reduction to dTDP-L-rhamnose. The module represents the soluble nucleotide-sugar supply pathway and treats downstream O-antigen, LPS, and specialized-polysaccharide assembly reactions as consumers, not as part of the biosynthetic module itself.

MODULE:dtdp_l_rhamnose_biosynthesisCOMPLETECONCRETEMetabolic Pathwaymodules/dtdp_l_rhamnose_biosynthesis.yaml
dTDP-rhamnose biosynthetic processGO:0019305
GO:0019305
dTDP-rhamnose biosynthetic process
GO:0019305 is the process term for the whole RmlABCD route and is accepted on every member gene review used as an exemplar here (E. coli K-12 RfbA/RfbB/RfbC/RfbD and P. putida KT2440 RfbA/RffG/RfbC/RmlC/RfbD).
PMID:11697907
Kinetic and crystallographic analyses support a sequential-ordered bi bi catalytic mechanism for Escherichia coli glucose-1-phosphate thymidylyltransferase.
Establishes RmlA as the first enzyme of dTDP-L-rhamnose biosynthesis, condensing dTTP and glucose 1-phosphate, from kinetics and crystal structures of the E. coli K-12 enzyme.
PMID:7517391
Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster.
The K-12 rfb cluster carries the four rhamnose-pathway genes rfbBDAC, and the O16 repeat unit contains alpha-L-rhamnose transferred by a separate rhamnosyltransferase, which sets the module's downstream boundary.
KEGG:ppu00523
Pseudomonas putida KT2440 polyketide sugar unit biosynthesis bucket
The KT2440 ppu00523 batch contains rmlC, PP_0500, rfbC and rfbD and also pulls in the adjacent rfbA/rffG early-step genes from ppu00525.
KEGG:ppu00525
Pseudomonas putida KT2440 acarbose/validamycin bucket
The ppu00525 bucket contributes the dTDP-glucose formation and dTDP-glucose 4,6-dehydration steps in KT2440, rather than a literal acarbose or validamycin pathway.
file:projects/P_PUTIDA/deep-research/PSEPK__dtdp_l_rhamnose_biosynthesis__ppu00523-deep-research-openscientist.md
OpenScientist module, pathway, and taxon review
The combined ppu00523/ppu00525 candidate set covers all four canonical reactions through the PP_1782-PP_1785 cluster. PP_0265 is a supported extra RmlC-family epimerase, whereas the in-vivo substrate and pathway assignment of the orphan RmlD-family paralog PP_0500 remain uncertain.

Scope and generalization: the RmlABCD route is conserved across Bacteria (Proteobacteria, Firmicutes, Actinobacteria, Cyanobacteria and others) and RmlC/RmlD homologs occur in some archaea, so the module is written species-neutrally and grounded to PANTHER families and bacterial PAINT nodes, with E. coli K-12 (experimentally characterised RfbA; rfb O16 cluster) and P. putida KT2440 (PP_1782-PP_1785 rfbC-rfbA-rfbD-rffG cluster plus the extra RmlC paralog PP_0265) as exemplars. Plants make UDP-L-rhamnose with trifunctional RHM enzymes instead and are outside this module. Representative members are exemplars, not simultaneously required pathway components. The KT2440 RmlD-like paralog PP_0500 lacks the NCBIfam TIGR01214 rmlD model and has no established substrate, so it is not used as an exemplar. Downstream O-antigen, LPS, capsule and secondary-metabolite assembly are product-use context outside the module boundary; the member gene reviews mark propagated polymer-level process terms (polysaccharide, LPS and O-antigen biosynthesis) as over-annotations of these precursor-supply enzymes. Location (cytosol, accepted on every member review) is omitted from this reusable reaction module because it adds no pathway discrimination. Family-function QC: PTHR43000 is a heterogeneous NAD(P)-dependent epimerase/dehydratase superfamily whose review leaves GO:0008460 UNRESOLVED at family scope while assessing the bacterial RmlB/RffG node PTN000042046 as SOUND, so the module keeps the verified PANTHER id for membership and cites that node; the resulting FAMILY_FUNCTION_UNREVIEWED warning is expected.

5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

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

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

9 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (13 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
rfba_glucose_1_phosphate_thymidylyltransferase rfbA (PSEPK)
UniProtKB:Q88LZ3
Family Representative
glucose-1-phosphate thymidylyltransferase activity
GO:0008879
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rfba_glucose_1_phosphate_thymidylyltransferase rfbA (ECOLI)
UniProtKB:P37744
Family Representative
glucose-1-phosphate thymidylyltransferase activity
GO:0008879
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rffg_dtdp_glucose_dehydratase rffG (PSEPK)
UniProtKB:Q88LZ1
Family Representative
dTDP-glucose 4,6-dehydratase activity
GO:0008460
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rffg_dtdp_glucose_dehydratase rfbB (ECOLI)
UniProtKB:P37759
Family Representative
dTDP-glucose 4,6-dehydratase activity
GO:0008460
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rmlc_rfbc_epimerase rmlC (PSEPK)
UniProtKB:Q88R69
Family Representative
dTDP-4-dehydrorhamnose 3,5-epimerase activity
GO:0008830
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rmlc_rfbc_epimerase rfbC (PSEPK)
UniProtKB:Q88LZ4
Family Representative
dTDP-4-dehydrorhamnose 3,5-epimerase activity
GO:0008830
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rmlc_rfbc_epimerase rfbC (ECOLI)
UniProtKB:P37745
Family Representative
dTDP-4-dehydrorhamnose 3,5-epimerase activity
GO:0008830
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rfbd_pp0500_reductase rfbD (PSEPK)
UniProtKB:Q88LZ2
Family Representative
dTDP-4-dehydrorhamnose reductase activity
GO:0008831
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rfbd_pp0500_reductase rfbD (ECOLI)
UniProtKB:P37760
Family Representative
dTDP-4-dehydrorhamnose reductase activity
GO:0008831
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rfba_glucose_1_phosphate_thymidylyltransferase glucose-1-phosphate thymidylyltransferase family
PANTHER:PTHR43532
Family
glucose-1-phosphate thymidylyltransferase activity
GO:0008879
Family Supported
Family review supports GO:0008879 FAMILY_WIDE. All reviewed members, in both subfamilies and in antibiotic or acarbose clusters, are glucose-1-phosphate thymidylyltransferases, and the activity is placed at the bacterial node that covers nearly the whole reference tree.
rffg_dtdp_glucose_dehydratase dTDP-glucose 4,6-dehydratase family
PANTHER:PTHR43000
Family
dTDP-glucose 4,6-dehydratase activity
GO:0008460
Family Function Unreviewed
Family review leaves GO:0008460 UNRESOLVED. The activity is established for the bacterial RmlB/RffG clade (node PTN000042046; subfamilies SF7 and SF47) but not family-wide: the family also holds UDP-sugar dehydratases, sulfoquinovose synthases, CDP- and GDP-sugar enzymes and sterol dehydrogenases. A SUBFAMILY_ONLY scope cannot be given safely because SF7 also contains eukaryotic TGDS and plant RHM leaves, and the fetched member list carries no subfamily assignments to check each reviewed member against. Members of the bacterial RmlB/RffG clade, including E. coli RfbB and P. putida RffG, carry the term on their own evidence.
rmlc_rfbc_epimerase dTDP-4-dehydrorhamnose 3,5-epimerase family
PANTHER:PTHR21047
Family
dTDP-4-dehydrorhamnose 3,5-epimerase activity
GO:0008830
Family Supported
Family review supports GO:0008830 FAMILY_WIDE. The 3,5-epimerase is the ancestral activity of the family and holds for the bacterial and archaeal RmlC enzymes. The actinomycete monoepimerases and the 2-deoxy-sugar epimerase are listed as member exceptions because PANTHER does not separate them by subfamily.
rfbd_pp0500_reductase dTDP-4-dehydrorhamnose reductase family
PANTHER:PTHR10491
Family
dTDP-4-dehydrorhamnose reductase activity
GO:0008831
Family Supported
Family review supports GO:0008831 FAMILY_WIDE. The reductase is the ancestral bacterial activity and holds for the RmlD enzymes. The eukaryotic MAT2B branch has lost catalysis and the antibiotic 4-ketoreductases act on other substrates; because PANTHER keeps everything in SF4, these are recorded as member exceptions, the MAT2B ones with the loss placed at PTN000051875. Uncharacterised bacterial RmlD-like paralogs outside rhamnose clusters (such as P. putida PP_0500) carry the term only as a prediction.

Gene-review completeness (9/9 grounded genes reviewed)

9 complete review(s) · 2 with deep research · 0 missing review · 7 reviewed but lacking deep research

Gene Review Complete Deep research
rfbA P37744 ✓ ✓ ✗
rfbA Q88LZ3 ✓ ✓ ✗
rfbB P37759 ✓ ✓ ✗
rfbC P37745 ✓ ✓ ✗
rfbC Q88LZ4 ✓ ✓ ✓
rfbD P37760 ✓ ✓ ✗
rfbD Q88LZ2 ✓ ✓ ✗
rffG Q88LZ1 ✓ ✓ ✓
rmlC Q88R69 ✓ ✓ ✗

Details

Context
bacteriaNCBITaxon:2
dTDP-L-rhamnose biosynthesisMetabolic Pathwaydtdp_l_rhamnose_biosynthesis
dTDP-rhamnose biosynthetic processGO:0019305
Context
bacteriaNCBITaxon:2

Connections

RfbA supplies dTDP-glucose for RffG dehydration.
RffG supplies the deoxy-keto dTDP-sugar for RmlC/RfbC.
The epimerase step supplies dTDP-4-dehydro-beta-L-rhamnose.
Part 1: dTDP-glucose formation
Glucose-1-phosphate thymidylyltransferaseReactionrfba_thymidylyltransferase_step

Annotons

RmlA/RfbA glucose-1-phosphate thymidylyltransferase
rfba_glucose_1_phosphate_thymidylyltransferase
Participant: Family: glucose-1-phosphate thymidylyltransferase family
Family:
glucose-1-phosphate thymidylyltransferase familyPANTHER:PTHR43532
Representative Members: rfbA (PSEPK)UniProtKB:Q88LZ3 rfbA (ECOLI)UniProtKB:P37744

Function

glucose-1-phosphate thymidylyltransferase activityGO:0008879
Substrates: dTTP alpha-D-glucose 1-phosphate
Products: dTDP-alpha-D-glucose diphosphate

Processes

dTDP-rhamnose biosynthetic processGO:0019305

Activates glucose 1-phosphate as dTDP-glucose for downstream deoxy-sugar conversion.

Part 2: dTDP-glucose dehydration
dTDP-glucose 4,6-dehydrataseReactionrffg_dtdp_glucose_dehydratase_step

Annotons

RmlB/RffG dTDP-glucose 4,6-dehydratase
rffg_dtdp_glucose_dehydratase
Participant: Family: dTDP-glucose 4,6-dehydratase family
Family:
dTDP-glucose 4,6-dehydratase familyPANTHER:PTHR43000
Representative Members: rffG (PSEPK)UniProtKB:Q88LZ1 rfbB (ECOLI)UniProtKB:P37759

Function

dTDP-glucose 4,6-dehydratase activityGO:0008460
Substrates: dTDP-alpha-D-glucose
Products: dTDP-4-dehydro-6-deoxy-alpha-D-glucose water
Cofactors: NAD+

Processes

dTDP-rhamnose biosynthetic processGO:0019305

Converts dTDP-glucose to the 4-keto-6-deoxy intermediate used by the RmlC/RfbC epimerase step.

Part 3: 3,5-epimerization
dTDP-4-dehydrorhamnose 3,5-epimeraseReactionrmlc_rfbc_epimerase_step

Annotons

RmlC/RfbC dTDP-4-dehydrorhamnose 3,5-epimerase
rmlc_rfbc_epimerase
Participant: Family: dTDP-4-dehydrorhamnose 3,5-epimerase family
Family:
dTDP-4-dehydrorhamnose 3,5-epimerase familyPANTHER:PTHR21047
Representative Members: rmlC (PSEPK)UniProtKB:Q88R69 rfbC (PSEPK)UniProtKB:Q88LZ4 rfbC (ECOLI)UniProtKB:P37745

Function

dTDP-4-dehydrorhamnose 3,5-epimerase activityGO:0008830
Substrates: dTDP-4-dehydro-6-deoxy-alpha-D-glucose
Products: dTDP-4-dehydro-beta-L-rhamnose

Processes

dTDP-rhamnose biosynthetic processGO:0019305

Epimerizes the deoxy-keto sugar nucleotide toward the L-rhamnose stereochemistry. PSEPK contains both PP_0265 and the cluster-encoded PP_1782 as representatives of this role.

Part 4: final reduction to dTDP-L-rhamnose
dTDP-4-dehydrorhamnose reductaseReactionrfbd_pp0500_reductase_step

Annotons

RmlD/RfbD dTDP-4-dehydrorhamnose reductase
rfbd_pp0500_reductase
Participant: Family: dTDP-4-dehydrorhamnose reductase family
Family:
dTDP-4-dehydrorhamnose reductase familyPANTHER:PTHR10491
Representative Members: rfbD (PSEPK)UniProtKB:Q88LZ2 rfbD (ECOLI)UniProtKB:P37760

Function

dTDP-4-dehydrorhamnose reductase activityGO:0008831
Substrates: dTDP-4-dehydro-beta-L-rhamnose NADPH
Products: dTDP-beta-L-rhamnose NADP+

Processes

dTDP-rhamnose biosynthetic processGO:0019305

Cluster-encoded reductase that completes dTDP-L-rhamnose synthesis. PP_0500 is excluded as a representative because its physiological substrate remains unresolved.