Pseudomonad lanthanide-switch PQQ alcohol oxidation

A reusable pseudomonad module coupling PedS2/PedR2 two-component signaling to metal-conditioned periplasmic alcohol oxidation. In the absence of usable lanthanides, phosphorylated PedR2 favors expression of the calcium-dependent PQQ alcohol dehydrogenase PedE. Lanthanide availability shifts the system toward the lanthanide-dependent paralog PedH. Both enzymes oxidize diverse alcohols in the periplasm and pass electrons to cytochrome c. PQQ biosynthesis, downstream aldehyde metabolism, and lanthanide uptake are adjacent systems and are outside this module. The enzymes carry the cytochrome-c alcohol dehydrogenase assignment, but their specific physiological cytochrome c partner in KT2440 remains inferred.

MODULE:pseudomonad_lanthanide_switch_pqq_alcohol_oxidationCOMPLETECONCRETEBiological Processmodules/pseudomonad_lanthanide_switch_pqq_alcohol_oxidation.yaml
phosphorelay signal transduction systemGO:0000160 alcohol metabolic processGO:0006066
PMID:28655819
Functional role of lanthanides in enzymatic activity and transcriptional regulation of pyrroloquinoline quinone-dependent alcohol dehydrogenases in Pseudomonas putida KT2440
Establishes the overlapping alcohol substrate ranges and contrasting calcium versus lanthanide requirements of PedE and PedH.
PMID:30158283
The PedS2/PedR2 two-component system is crucial for the rare earth element switch in Pseudomonas putida KT2440
Establishes PedS2/PedR2 as the central phosphorelay controlling inverse pedE and pedH expression in response to lanthanide availability.
GO:0000160
phosphorelay signal transduction system
Defines the sensor-kinase and response-regulator relationship.
GO:0052934
alcohol dehydrogenase (cytochrome c) activity
Defines the shared catalytic activity of PedE and PedH.

Scope is deliberately pseudomonad (CONCRETE, NCBITaxon:286) rather than generalized to all lanthanide switches. A calcium/lanthanide switch between PQQ dehydrogenases also operates in methylotrophs such as Methylorubrum extorquens (MxaFI versus XoxF methanol dehydrogenases), but that system is an analogous rather than homologous circuit: its enzymes are methanol dehydrogenases of a different PANTHER subfamily (PTHR32303:SF4, cytochrome cL-linked), and its control runs through other regulators (MxbD/MxbM, MxcQ/MxcE) with XoxF itself required for the switch. Merging the two would assert a shared PedS2/PedR2 regulatory architecture that has not been shown outside Pseudomonas. The methylotroph switch is better modeled as a sibling module, and the M. extorquens lanthanide-dependent ethanol dehydrogenase ExaF, although in the same SF20 subfamily as PedE and PedH, is not added as a member because its regulation is not PedS2/PedR2-mediated. P. putida KT2440 proteins are exemplars of the Ped system, not species-specific required members. PANTHER groundings were adopted from the maintainer grounding pass and checked against interpro/panther/panther.obo and the UniProt PANTHER cross-references: PedS2 is PTHR24421 (SF10), PedR2 is PTHR43214 (SF43), and PedE and PedH are both PTHR32303:SF20. Each family id grounds only the generic activity (sensor kinase, response regulator, cytochrome c-linked alcohol dehydrogenase), as recorded in the FamilyReviews; the lanthanide responsiveness of PedS2, the pedE/pedH targets of PedR2, and the metal dependence that separates the PedE and PedH variants are member-level properties supported by PMID:28655819 and PMID:30158283. Because SF20 does not separate the two metal variants, each variant keeps only its own paralog as representative member. The PedS2/PedR2 bundle is a simple two-component instance of MODULE:two_component_relay without the Hpt tier; it declares `conforms_to` that template WITH_DEVIATIONS for the collapsed Hpt step, as the template prescribes and as the Kdp and Ntr modules do. PedH-dependent feedback on pedE/pedH transcription is retained as a knowledge gap rather than assigning PedH a transcription-regulatory molecular function.

7Nodes
4Parts
1Variant Sets
2Variants
4Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

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

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

3 conformance issue(s):

  • ped_phosphorelay → two_component_relay [info]
    tier count 2 does not match template 3 (two_component_relay)
  • ped_phosphorelay → two_component_relay [info]
    tier 2 function GO:0000156 does not match template GO:0009927
  • ped_phosphorelay → two_component_relay [info]
    connection topology does not match the template motif

Function consistency and core coverage

4 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (8 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
peds2_sensor_kinase PedS2 (Pseudomonas putida KT2440)
UniProtKB:Q88JH8
Family Representative
phosphorelay sensor kinase activity
GO:0000155
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pedr2_response_regulator PedR2/ExaE (Pseudomonas putida KT2440)
UniProtKB:Q88JH7
Family Representative
phosphorelay response regulator activity
GO:0000156
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pede_alcohol_dehydrogenase PedE (Pseudomonas putida KT2440)
UniProtKB:Q88JH5
Family Representative
alcohol dehydrogenase (cytochrome c) activity
GO:0052934
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pedh_alcohol_dehydrogenase PedH (Pseudomonas putida KT2440)
UniProtKB:Q88JH0
Family Representative
alcohol dehydrogenase (cytochrome c) activity
GO:0052934
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
peds2_sensor_kinase HisKA_3 sensor histidine kinase family (PedS2 member)
PANTHER:PTHR24421
Family
phosphorelay sensor kinase activity
GO:0000155
Family Supported
Family review supports GO:0000155 FAMILY_WIDE. Every characterized member is a two-component sensor histidine kinase with the HisKA_3 phosphoacceptor and HATPase_c catalytic domains, and characterized members across subfamilies (NarX, NarQ, UhpB, DesK, PedS2) phosphorylate a cognate response regulator. Sensor input and partner regulator are member-specific and are not covered by this assessment.
pedr2_response_regulator NarL/FixJ-type response regulator family (PedR2 member)
PANTHER:PTHR43214
Family
phosphorelay response regulator activity
GO:0000156
Family Supported
Family review supports GO:0000156 FAMILY_WIDE. All members share the CheY-like receiver domain with the conserved phospho-accepting aspartate (Asp59 in NarL), and characterized members across subfamilies (NarL, NarP, UhpA, RcsB, DegU, PedR2) are regulated by phosphotransfer from a cognate kinase or Hpt. PAINT does not currently assert this term at any node in the family.
pede_alcohol_dehydrogenase calcium-dependent PedE-type quinoprotein ethanol dehydrogenase
PANTHER:PTHR32303:SF20
Family
alcohol dehydrogenase (cytochrome c) activity
GO:0052934
Family Supported
Family review supports GO:0052934 for PANTHER:PTHR32303:SF20. Cytochrome c-linked oxidation of primary and secondary alcohols is the function of the characterized SF20 type I alcohol dehydrogenases, whether calcium-dependent (PedE, ExaA) or lanthanide-dependent (PedH, ExaF). It is not safe for SF4, whose glucose, quinate and glycerol dehydrogenases reduce ubiquinone and whose methanol dehydrogenases are the distinct cytochrome cL-linked enzymes, nor for SF10 (BamB). The catalytic metal is not determined by subfamily, so this assessment does not license calcium- or lanthanide-specific claims.
pedh_alcohol_dehydrogenase lanthanide-dependent PedH-type quinoprotein ethanol dehydrogenase
PANTHER:PTHR32303:SF20
Family
alcohol dehydrogenase (cytochrome c) activity
GO:0052934
Family Supported
Family review supports GO:0052934 for PANTHER:PTHR32303:SF20. Cytochrome c-linked oxidation of primary and secondary alcohols is the function of the characterized SF20 type I alcohol dehydrogenases, whether calcium-dependent (PedE, ExaA) or lanthanide-dependent (PedH, ExaF). It is not safe for SF4, whose glucose, quinate and glycerol dehydrogenases reduce ubiquinone and whose methanol dehydrogenases are the distinct cytochrome cL-linked enzymes, nor for SF10 (BamB). The catalytic metal is not determined by subfamily, so this assessment does not license calcium- or lanthanide-specific claims.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • ped_phosphorelay ⊣ pedh_lanthanide_oxidation [input]
    ped_phosphorelay is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (4/4 grounded genes reviewed)

4 complete review(s) · 4 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
exaE Q88JH7 ✓ ✓ ✓
pedE Q88JH5 ✓ ✓ ✓
pedH Q88JH0 ✓ ✓ ✓
PP_2671 Q88JH8 ✓ ✓ ✓

Details

Context
PseudomonasNCBITaxon:286
Pseudomonad lanthanide-switch PQQ alcohol oxidationBiological Processpseudomonad_lanthanide_switch_pqq_alcohol_oxidation
phosphorelay signal transduction systemGO:0000160 alcohol metabolic processGO:0006066
Context
PseudomonasNCBITaxon:286

Connections

ped_phosphorelay -> pede_calcium_oxidation Positively Regulates
Phosphorylated PedR2 promotes the calcium-dependent PedE branch in the lanthanide-free state.
PedR2 contributes to repression of the PedH branch without lanthanides.
Part 1: PedS2/PedR2 His-Asp phosphorelay
PedS2/PedR2 phosphorelaySignaling Pathwayped_phosphorelay

The sensor histidine kinase PedS2 autophosphorylates according to the lanthanide-responsive input and phosphorylates the conserved receiver aspartate of PedR2, which effects the transcriptional switch. This is a simple two-component instance of the MODULE:two_component_relay motif without its histidine-phosphotransfer (Hpt) tier: PedS2 has HAMP, histidine-kinase and HATPase domains but no Hpt or receiver domain, so it transfers phosphate directly to PedR2.

Connections

PedS2 transfers its phosphoryl group to the PedR2 receiver aspartate.
Part 1: lanthanide-responsive PedS2 sensor signaling
PedS2 sensor-kinase signalingSignaling Pathwaypeds2_sensor_signaling

Annotons

PedS2 phosphorelay sensor kinase
peds2_sensor_kinase
Participant: Family: HisKA_3 sensor histidine kinase family (PedS2 member)
Family:
HisKA_3 sensor histidine kinase family (PedS2 member)PANTHER:PTHR24421 The PANTHER family grounds the conserved phosphorelay sensor kinase activity only. Lanthanide responsiveness is a property of PedS2 itself, not of the family or of its subfamily SF10, which also holds nitrate (NarQ) and oxygen (NreB) sensors.
Representative Members: PedS2 (Pseudomonas putida KT2440)UniProtKB:Q88JH8

Function

phosphorelay sensor kinase activityGO:0000155

Processes

phosphorelay signal transduction systemGO:0000160

Locations

membraneGO:0016020

Controls PedR2 phosphorylation according to the lanthanide-responsive physiological input; the direct molecular ligand remains unresolved.

Part 2: PedR2 transcriptional switch output
PedR2-dependent transcriptional controlBiological Processpedr2_transcriptional_output

Annotons

PedR2 phosphorelay response regulator
pedr2_response_regulator
Participant: Family: NarL/FixJ-type response regulator family (PedR2 member)
Family:
NarL/FixJ-type response regulator family (PedR2 member)PANTHER:PTHR43214 The PANTHER family grounds the conserved receiver plus LuxR-HTH response regulator activity. Control of pedE and pedH is specific to PedR2; subfamily SF43 also holds methylotroph methanol dehydrogenase regulators with different input and target logic.
Representative Members: PedR2/ExaE (Pseudomonas putida KT2440)UniProtKB:Q88JH7

Function

phosphorelay response regulator activityGO:0000156

Processes

regulation of DNA-templated transcriptionGO:0006355

Phosphorylated PedR2 activates pedE expression and contributes to pedH repression when usable lanthanides are absent.

Part 2: metal-conditioned periplasmic PQQ alcohol oxidation
Alternative PedE/PedH alcohol oxidationReactionpqq_alcohol_oxidation
Variant set: Ped alcohol-dehydrogenase metal variants by catalytic metal availability (One Or More)
Calcium-dependent PedE alcohol oxidationReactionpede_calcium_oxidation

Annotons

Calcium-dependent PQQ alcohol dehydrogenase PedE
pede_alcohol_dehydrogenase
Participant: Family: calcium-dependent PedE-type quinoprotein ethanol dehydrogenase
Family:
calcium-dependent PedE-type quinoprotein ethanol dehydrogenasePANTHER:PTHR32303:SF20 PANTHER subfamily SF20 grounds the shared cytochrome c-linked alcohol dehydrogenase activity. It does not separate calcium- from lanthanide-dependent members (PedE and PedH are both SF20), so the calcium branch is identified by the representative member and its experimental metal dependence.
Representative Members: PedE (Pseudomonas putida KT2440)UniProtKB:Q88JH5

Function

alcohol dehydrogenase (cytochrome c) activityGO:0052934
Substrates: alcohol oxidized cytochrome c
Products: aldehyde or ketone reduced cytochrome c

Processes

alcohol metabolic processGO:0006066

Locations

periplasmic spaceGO:0042597

Performs PQQ-dependent alcohol oxidation when calcium is available and the lanthanide switch favors pedE expression.

Lanthanide-dependent PedH alcohol oxidationReactionpedh_lanthanide_oxidation

Annotons

Lanthanide-dependent PQQ alcohol dehydrogenase PedH
pedh_alcohol_dehydrogenase
Participant: Family: lanthanide-dependent PedH-type quinoprotein ethanol dehydrogenase
Family:
lanthanide-dependent PedH-type quinoprotein ethanol dehydrogenasePANTHER:PTHR32303:SF20 PANTHER subfamily SF20 grounds the shared cytochrome c-linked alcohol dehydrogenase activity. It does not separate lanthanide- from calcium-dependent members, so the lanthanide branch is identified by the representative member and its experimental metal dependence.
Representative Members: PedH (Pseudomonas putida KT2440)UniProtKB:Q88JH0

Function

alcohol dehydrogenase (cytochrome c) activityGO:0052934
Substrates: alcohol oxidized cytochrome c
Products: aldehyde or ketone reduced cytochrome c

Processes

alcohol metabolic processGO:0006066

Locations

periplasmic spaceGO:0042597

Performs PQQ-dependent alcohol oxidation when usable lanthanides are available and the switch favors pedH.