identifier: METPO:1003004
label: obligately alkaphilic
definition: A pH growth preference in which an organism requires alkaline conditions
  (typically pH above 8.5) for growth and cannot grow at neutral or acidic pH.
definition_source: DOI:10.3389/fbioe.2015.00075
trait_category: ENVIRONMENT
term_kind: CLASS
mapping_status: REVIEWED
parent_traits:
- METPO:1003000
synonyms:
- synonym_text: obligate alkaliphile
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
- synonym_text: obligate alkaphilic
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
- synonym_text: obligately alkaliphilic
  synonym_type: EXACT_SYNONYM
  source: metpo.owl
created_by: Luke Wang
evidence:
- reference: DOI:10.3389/fbioe.2015.00075
  snippet: grow only at pH values of ~pH 9 and above
  notes: Supports the obligate alkaliphile definition.
canonical_examples:
- taxon_id: NCBITaxon:2257
  taxon_label: Natronomonas pharaonis
  note: "Soda-lake haloalkaliphilic archaeon (pH optimum ~8.5, alkaline tolerance to ~pH 11). Halalkalibacterium halodurans C-125 (ex-Bacillus halodurans) is the classic non-halophilic obligate alkaliphile."
  reference: https://pmc.ncbi.nlm.nih.gov/articles/PMC1240075/
causal_graphs:
- graph_id: obligately_alkaphilic_sodium_cycle_homeostasis
  title: Obligate alkaliphily sodium-cycle pH homeostasis mechanism
  description: Evidence-backed causal sketch linking obligate alkaliphily to high
    external pH, Na+/H+ antiport, and cytoplasmic proton accumulation.
  nodes:
  - node_id: obligately_alkaphilic_trait
    label: obligately alkaphilic
    node_type: TRAIT
    grounding: METPO:1003004
    description: Growth requires alkaline pH and does not extend to neutral or acidic
      pH.
  - node_id: alkaline_external_ph
    label: alkaline external pH
    node_type: ENVIRONMENTAL_FACTOR
    description: External pH near or above pH 9.
    grounding: PATO:0001430
  - node_id: sodium_ion
    label: sodium ion
    node_type: CHEMICAL
    grounding: CHEBI:29101
    description: Sodium ion participating in alkaliphile sodium cycles.
  - node_id: proton
    label: proton
    node_type: CHEMICAL
    grounding: CHEBI:15378
    description: Hydrogen ion imported or retained to acidify the cytoplasm.
  - node_id: sodium_proton_antiporter
    label: Na+/H+ antiporter
    node_type: GENE_OR_PROTEIN
    description: Antiporter exchanging sodium ions and protons during alkaline pH
      homeostasis.
    grounding: UniProtKB:A0A068T423
  - node_id: cytoplasmic_ph_homeostasis
    label: cytoplasmic pH homeostasis
    node_type: BIOLOGICAL_PROCESS
    description: Maintenance of intracellular pH below strongly alkaline external
      pH.
    grounding: GO:0051453
  - node_id: proton_coupled_atp_synthase
    label: proton-coupled ATP synthase
    node_type: GENE_OR_PROTEIN
    description: ATP synthase that remains proton-coupled in respiratory alkaliphiles.
  - node_id: trkah_transport_system
    label: TrkAH K+ uptake system
    node_type: GENE_OR_PROTEIN
    description: Potassium uptake system contributing to pH homeostasis and membrane
      potential adjustment.
  - node_id: cation_proton_antiporter
    label: monovalent cation/proton antiporters
    node_type: GENE_OR_PROTEIN
    description: CPA/Mrp and Nha family antiporters regulating H+ influx and Na+ efflux
      under stress.
  - node_id: secondary_cell_wall_polymers
    label: secondary cell wall polymers / S-layer
    node_type: CELLULAR_LOCALIZATION
    description: Cell-surface polymers and S-layer proteins developed by alkaliphilic
      microbes.
  - node_id: net_negative_surface_charge
    label: net negative surface charge
    node_type: QUALITY
    description: Increased negative charge on cellular surfaces that attracts external
      protons.
  - node_id: anionic_membrane_phospholipids
    label: anionic membrane phospholipids (PG/PC/CL)
    node_type: CHEMICAL
    description: Phosphatidylglycerol, phosphatidylcholine, and cardiolipin enriched
      under high pH.
  - node_id: acetate_anion
    label: acetate anion
    node_type: CHEMICAL
    description: Dissociated form of acetic acid favored at high pH.
  - node_id: acetate_transmembrane_diffusion
    label: transmembrane diffusion of acetate
    node_type: BIOLOGICAL_PROCESS
    description: Passive diffusion of protonated acetic acid across the membrane,
      prevented at high pH.
  edges:
  - subject: alkaline_external_ph
    predicate: is required for
    object: obligately_alkaphilic_trait
    description: Obligate alkaliphiles grow only under alkaline pH conditions.
    evidence:
    - reference: DOI:10.3389/fbioe.2015.00075
      snippet: grow only at pH values of ~pH 9 and above
      notes: Review explicitly defines obligate alkaliphiles by alkaline pH restriction.
  - subject: alkaline_external_ph
    predicate: challenges
    object: cytoplasmic_ph_homeostasis
    description: High external pH requires cells to maintain cytoplasmic pH below
      the medium.
    evidence:
    - reference: DOI:10.1038/nrmicro2549
      snippet: below an external pH range of 9.5-11.0
      notes: Supports cytoplasmic pH control under extreme alkaline external pH.
    predicate_id: METPO:2007406
  - subject: sodium_proton_antiporter
    predicate: exports
    object: sodium_ion
    description: Na+/H+ antiport couples sodium efflux to proton accumulation.
    evidence:
    - reference: DOI:10.1016/S0005-2728(00)00285-1
      snippet: Na+ efflux
      notes: Supports sodium efflux as part of the alkaliphile Na+ cycle.
    predicate_id: METPO:2000209
  - subject: sodium_proton_antiporter
    predicate: accumulates
    object: proton
    description: Na+/H+ antiport achieves net proton accumulation for alkaline pH
      homeostasis.
    evidence:
    - reference: DOI:10.1016/S0005-2728(00)00285-1
      snippet: achieve net H+ accumulation
      notes: Supports proton accumulation by antiporters in alkaliphiles.
    predicate_id: METPO:2000210
  - subject: proton_coupled_atp_synthase
    predicate: regulates
    object: obligately_alkaphilic_trait
    description: Proton-coupled ATP synthesis at very high pH creates a bioenergetic
      constraint requiring alkaliphile-specific adaptations.
    evidence:
    - reference: DOI:10.1016/j.bbabio.2010.02.028
      snippet: robust H+-coupled ATP synthesis at external pH values > 10
      notes: Supports the proton-coupled ATP synthesis challenge in alkaliphiles.
    predicate_id: RO:0002211
  - subject: cytoplasmic_ph_homeostasis
    predicate: enables
    object: obligately_alkaphilic_trait
    description: Growth at obligately alkaline pH depends on maintaining intracellular
      pH compatible with cell function.
    evidence:
    - reference: DOI:10.1016/S0005-2728(00)00285-1
      snippet: pH homeostasis ... appears to set the upper pH limit for growth
      notes: Supports pH homeostasis as growth-limiting for alkaliphilic Bacillus.
    predicate_id: RO:0002327
  - subject: trkah_transport_system
    predicate: contributes to
    object: cytoplasmic_ph_homeostasis
    description: TrkAH K+ uptake supports cytoplasmic pH homeostasis under alkaline
      conditions.
    evidence:
    - reference: DOI:10.1128/AEM.00145-24
      notes: The TrkAH transport system is responsible for the uptake of K+ ... and
        maintaining pH homeostasis.
    predicate_id: RO:0002326
  - subject: cation_proton_antiporter
    predicate: is required for
    object: obligately_alkaphilic_trait
    description: Monovalent cation/proton antiporters are essential for growth of
      alkaliphilic bacteria under stress.
    evidence:
    - reference: DOI:10.1128/AEM.00145-24
      notes: Monovalent cation/proton antiporters ... are essential for the growth
        of various halophilic and alkaliphilic bacteria under stress conditions.
  - subject: secondary_cell_wall_polymers
    predicate: increases
    object: net_negative_surface_charge
    description: Secondary cell wall polymers and S-layer proteins enhance net negative
      surface charge.
    evidence:
    - reference: DOI:10.3389/fmicb.2022.1034164
      notes: the second cell wall polymers (SCWPs), such as S-layer protein ... enhance
        net negative charges on cellular surfaces.
    predicate_id: RO:0002213
  - subject: net_negative_surface_charge
    predicate: increases attraction to
    object: proton
    description: Net negative surface charge increases attraction of external protons
      toward the cell surface.
    evidence:
    - reference: DOI:10.3389/fmicb.2022.1034164
      notes: net negative charges on cellular surfaces that increase attraction to
        external protons.
  - subject: alkaline_external_ph
    predicate: increases abundance of
    object: anionic_membrane_phospholipids
    description: High external pH increases relative abundance of PG, PC, and cardiolipin
      (membrane remodeling).
    evidence:
    - reference: DOI:10.3389/fmicb.2022.1034164
      notes: It increased the relative abundance of phosphatidylglycerol (PG), phosphatidylcholine
        (PC), and cardiolipin (CL) in response to high pH.
  - subject: alkaline_external_ph
    predicate: causes
    object: acetate_anion
    description: Alkaline conditions (>pH 9) favor dissociation of acetic acid to
      the acetate anion.
    evidence:
    - reference: DOI:10.3389/fmicb.2023.1233691
      notes: High pH favors the dissociation of acetic acid to its anion (CH3COO-),
        preventing transmembrane diffusion.
    predicate_id: biolink:causes
  - subject: acetate_anion
    predicate: prevents
    object: acetate_transmembrane_diffusion
    description: Acetate anion at high pH cannot diffuse passively across the membrane.
    evidence:
    - reference: DOI:10.3389/fmicb.2023.1233691
      notes: High pH favors the dissociation of acetic acid to its anion (CH3COO-),
        preventing transmembrane diffusion.
    predicate_id: RO:0002212
curation_history:
- timestamp: '2026-05-05T01:35:46.938910+00:00'
  curator: seed_from_metpo
  action: SEEDED_FROM_METPO
  changes: imported from data/raw/metpo.owl (CLASS)
  llm_assisted: false
- timestamp: '2026-05-11T00:00:00-07:00'
  curator: codex
  action: CURATED_WITH_LITERATURE
  changes: Reviewed obligately alkaphilic trait and added DOI-backed evidence and
    causal graph for sodium-cycle alkaline pH homeostasis and ATP synthase bioenergetic
    constraints.
  llm_assisted: true
- timestamp: '2026-05-20T03:35:30Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002327×1).
  llm_assisted: true
- timestamp: '2026-05-23T21:30:06Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2007406×1).
  llm_assisted: true
- timestamp: '2026-05-24T04:38:00Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (GO:0030641×1).
  llm_assisted: true
- timestamp: '2026-05-24T05:05:14Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (UniProtKB:A0A068T423×1).
  llm_assisted: true
- timestamp: '2026-05-24T08:14:32Z'
  curator: claude
  action: GROUND_CAUSAL_NODES
  changes: Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv
    (PATO:0001429×1).
  llm_assisted: true
- timestamp: '2026-05-26T05:00:47Z'
  curator: claude
  action: RENAME_PREDICATE_LABELS
  changes: 'Renamed 1 causal-edge predicate label(s) to align with existing groundings:
    constrains → regulates ×1.'
  llm_assisted: true
- timestamp: '2026-05-26T05:00:50Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002211×1).
  llm_assisted: true
- timestamp: '2026-06-15T07:20:36Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 causal-node grounding(s) (obsolete/wrong GO -> corrected, verified
    vs OAK).
  llm_assisted: true
- timestamp: '2026-06-15T07:21:43Z'
  curator: claude
  action: FIX_NODE_GROUNDING_CURIE
  changes: Overwrote 1 pH causal-node grounding(s) to corrected PATO CURIEs (phase-2;
    verified vs OAK).
  llm_assisted: true
- timestamp: '2026-06-16T06:30:55Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (METPO:2000209×1, METPO:2000210×1).
  llm_assisted: true
- timestamp: '2026-06-23T00:00:00Z'
  curator: claude
  action: ENRICH_CAUSAL_GRAPH
  changes: Added 7 evidence-backed generic edges (7 new nodes) from the deep-research
    report.
  llm_assisted: true
- timestamp: '2026-06-24T17:21:10Z'
  curator: claude
  action: GROUND_CAUSAL_PREDICATES
  changes: Grounded 4 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv
    (RO:0002326×1, RO:0002213×1, biolink:causes×1, RO:0002212×1).
  llm_assisted: true