identifier: traitmech:000432
label: DS-8 system
definition: A phage defense system in which an organism possesses the single-gene
  DefensePredictor-discovered system 8 locus cataloged with working_id MNAC and whose
  plasmid expression in E. coli MG1655 reduced bacteriophage plaquing.
definition_source: DOI:10.1126/science.adv7924
trait_category: GENOMICS
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000209
synonyms:
- synonym_text: DS-8
  synonym_type: EXACT_SYNONYM
  source: DOI:10.1126/science.adv7924
- synonym_text: MNAC
  synonym_type: RELATED_SYNONYM
  source: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
- synonym_text: DS-8__DS-8
  synonym_type: RELATED_SYNONYM
  source: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
evidence:
- reference: DOI:10.1126/science.adv7924
  snippet: To test for anti-phage defense, we placed each TU with its predicted native
    promoter region on a low-copy number plasmid in E. coli MG1655 and challenged
    these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In
    total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced
    the efficiency of plating (EOP) at least ten-fold relative to an empty vector
    control strain
  notes: DeWeirdt et al. experimentally validated 42 predicted transcriptional units
    as phage-defense systems in E. coli.
- reference: DOI:10.1126/science.adv7924
  snippet: First, we investigated DS-8, a single protein system containing a metallophosphatase
    domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase
    that cleaves cGAMP to modulate cGAS-STING immunity signaling
  notes: DeWeirdt et al. identify DS-8 as a single-protein metallophosphatase-domain
    system.
- reference: DOI:10.1126/science.adv7924
  snippet: Mutating either of two predicted catalytic residues in the metallophosphatase
    domain or a residue likely critical to NACHT ATPase activity completely ablated
    defense by DS-8, indicating that both domains and metallophosphatase activity
    are essential for protection
  notes: DeWeirdt et al. report that predicted metallophosphatase catalytic-residue
    and NACHT ATPase-residue mutations ablated DS-8 defense.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
  snippet: "MNAC\tNZ_RRWS01000004.1\tGCF_003892555.1\t-\tTrue\tFalse\tFalse\tTrue\t\
    DefensePredictor hits\t83803\t86847\tmetallophosphoesterase\tWP_032203427.1\t\
    9.394229333124514\t6.212606095751518\tTrue\tTrue\tPredicted novel defense gene\t\
    DS-8"
  notes: The final Science supplementary Table S6 maps working_id MNAC to DS_name
    DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1
    positions 83803-86847 with product accession WP_032203427.1.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tMNAC\t24-03-08\t\
    24-03-08_MNAC_GHOS_BRNT_IMPD.png\t1\t10\tY\t100\t5.6020599913279625\tTrue\t\t\t\
    LB\t37"
  notes: The final Science supplementary Table S7 reports an MNAC assay row with a
    Bas1 phage readout and a -log(EOP) value of 5.602.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t3000000\t\
    MNAC\tK375A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t6\t3\t\t\
    3000000\t0"
  notes: The final Science supplementary Table S7 reports the MNAC K375A Bas1 mutant
    row with a -log(EOP) value of 0.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t3000000\t\
    MNAC\tN84A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t6\t2\t\t\
    2000000\t0.1760912591"
  notes: The final Science supplementary Table S7 reports the MNAC N84A Bas1 mutant
    row with a -log(EOP) value of 0.176.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
  snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t3000000\t\
    MNAC\tD52A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t6\t4\t\t\
    4000000\t-0.1249387366"
  notes: The final Science supplementary Table S7 reports the MNAC D52A Bas1 mutant
    row with a -log(EOP) value of -0.125.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "MNAC\tDS-8\tTrue"
  notes: The final Science supplementary Table S8 maps MNAC to replicated display
    name DS-8.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "MNAC\t1.0\t1014.0\tWP_032203427.1\tMetallophosphatase\t5KAR_A\tAcid sphingomyelinase-like\
    \ phosphodiesterase 3b; phosphoesterase, extracellular, membrane\thhpred_8521728.hhr\t\
    1.0\t275.0\t0.997\t2024-04-16 00:00:00"
  notes: The final Science supplementary Table S8 reports a metallophosphatase HHpred
    hit for WP_032203427.1 in MNAC.
- reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
  snippet: "MNAC\t1.0\t1014.0\tWP_032203427.1\tNACHT\t8FML_A\tBaculoviral IAP repeat-containing\
    \ protein 1e; Inflammasome, Innate immunity, Bacterial ligand, host-pathogen interaction,\
    \ Protein complex, IMMUNE SYSTEM\thhpred_8521728.hhr\t331.0\t734.0\t1.0\t2024-04-16\
    \ 00:00:00"
  notes: The final Science supplementary Table S8 reports a NACHT HHpred hit for WP_032203427.1
    in MNAC.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
  snippet: '| DS-8 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine learning
    model to discover novel prokaryotic immune systems | '
  notes: The pinned DefenseFinder article registry maps the DS-8 source key to the
    preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since been
    published in Science.
- reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
  snippet: '| DS-8__DS-8                                       |                                                  |
    DS-8                   | Custom                  | 200    |'
  notes: The pinned DefenseFinder HMM inventory records DS-8__DS-8 as a custom DS-8
    profile.
causal_graphs:
- graph_id: ds_8_locus_reduces_phage_plaquing
  title: DS-8 locus reduces bacteriophage plaquing
  description: Conservative system-level sketch linking the single-gene DS-8 locus
    to reduced bacteriophage plaquing without resolving DS-8 component function or
    effector activity.
  scope_status: NONMECHANISTIC
  scope_notes: The graph captures DS-8 as the validated MNAC transcriptional unit
    with one product accession and with a DefenseFinder DS-8 profile row. It does
    not assert native host breadth, exact profile-to-protein correspondence, the direct
    viral trigger or cyclic-nucleotide substrate, the exact NACHT-mediated activation
    step, relationship to NLR-like bNACHT systems, phage target breadth, or DefenseFinder
    rule-level detection criteria.
  nodes:
  - node_id: ds_8_locus
    label: DS-8 locus
    node_type: GENETIC_ELEMENT
    description: A single-gene DefensePredictor-discovered system locus represented
      in the pinned DefenseFinder HMM inventory by one DS-8 custom profile.
  - node_id: reduced_phage_plaquing
    label: reduced bacteriophage plaquing
    node_type: BIOLOGICAL_PROCESS
    description: Reduced efficiency of plaquing by bacteriophage Bas1 in cells carrying
      cloned MNAC.
  - node_id: ds_8_system_trait
    label: DS-8 system
    node_type: TRAIT
    grounding: traitmech:000432
    description: Possession of a genome-encoded DS-8 phage-defense system.
  - node_id: phage_defense_system
    label: phage defense system
    node_type: TRAIT
    grounding: traitmech:000209
    description: Possession of one or more genome-encoded immune systems that inhibit
      bacteriophage infection.
  edges:
  - subject: ds_8_locus
    predicate: contributes to
    predicate_id: RO:0002326
    object: reduced_phage_plaquing
    description: The DS-8/MNAC locus contributes to reduced bacteriophage plaquing
      when plasmid expressed.
    evidence:
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "MNAC\tNZ_RRWS01000004.1\tGCF_003892555.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t83803\t86847\tmetallophosphoesterase\tWP_032203427.1\t\
        9.394229333124514\t6.212606095751518\tTrue\tTrue\tPredicted novel defense\
        \ gene\tDS-8"
      notes: The final Science supplementary Table S6 maps working_id MNAC to DS_name
        DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1
        positions 83803-86847 with product accession WP_032203427.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tMNAC\t\
        24-03-08\t24-03-08_MNAC_GHOS_BRNT_IMPD.png\t1\t10\tY\t100\t5.6020599913279625\t\
        True\t\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports an MNAC assay row with
        a Bas1 phage readout and a -log(EOP) value of 5.602.
  - subject: reduced_phage_plaquing
    predicate: confers
    predicate_id: METPO:2007700
    object: ds_8_system_trait
    description: DS-8-mediated phage plaquing reduction realizes the DS-8 system trait.
    evidence:
    - reference: DOI:10.1126/science.adv7924
      snippet: First, we investigated DS-8, a single protein system containing a metallophosphatase
        domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase
        that cleaves cGAMP to modulate cGAS-STING immunity signaling
      notes: DeWeirdt et al. identify DS-8 as a single-protein metallophosphatase-domain
        system.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
      snippet: "MNAC\tNZ_RRWS01000004.1\tGCF_003892555.1\t-\tTrue\tFalse\tFalse\t\
        True\tDefensePredictor hits\t83803\t86847\tmetallophosphoesterase\tWP_032203427.1\t\
        9.394229333124514\t6.212606095751518\tTrue\tTrue\tPredicted novel defense\
        \ gene\tDS-8"
      notes: The final Science supplementary Table S6 maps working_id MNAC to DS_name
        DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1
        positions 83803-86847 with product accession WP_032203427.1.
    - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
      snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tMNAC\t\
        24-03-08\t24-03-08_MNAC_GHOS_BRNT_IMPD.png\t1\t10\tY\t100\t5.6020599913279625\t\
        True\t\t\tLB\t37"
      notes: The final Science supplementary Table S7 reports an MNAC assay row with
        a Bas1 phage readout and a -log(EOP) value of 5.602.
  - subject: ds_8_system_trait
    predicate: is a
    predicate_id: rdfs:subClassOf
    object: phage_defense_system
    description: DS-8 system possession is a phage-defense-system trait.
    evidence:
    - reference: DOI:10.1126/science.adv7924
      snippet: To test for anti-phage defense, we placed each TU with its predicted
        native promoter region on a low-copy number plasmid in E. coli MG1655 and
        challenged these strains with a panel of 24 diverse E. coli phages (Fig. 3;
        fig. S2). In total, 42 (45% of 94) of the cloned TUs produced smaller plaque
        sizes or reduced the efficiency of plating (EOP) at least ten-fold relative
        to an empty vector control strain
      notes: DeWeirdt et al. validate DSs as anti-phage systems.
    - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
      snippet: '| DS-8 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine
        learning model to discover novel prokaryotic immune systems | '
      notes: The pinned DefenseFinder article registry maps the DS-8 source key to
        the preprint DOI for the DeWeirdt et al. DefensePredictor study, which has
        since been published in Science.
discussions:
- discussion_id: ds-8-defensefinder-model-gap
  prompt: Resolve DS-8 native host breadth, DS-8 profile-to-protein mapping, sensitive-phage
    breadth, direct cyclic-nucleotide substrate, NACHT-mediated activation route,
    relationship to NLR-like bNACHT systems, and rule-level detection criteria before
    minting narrower DS-8 mechanism children.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: DeWeirdt et al. support DS-8 as the defensive MNAC transcriptional unit
    that reduced Bas1 plaquing when cloned in E. coli MG1655, identify DS-8 as a single-protein
    system with metallophosphatase and NACHT domains, and report that D52A, N84A,
    and K375A mutations ablated Bas1 protection. The pinned DefenseFinder HMM inventory
    records one DS-8 profile row. The pinned rules table has no DS-8 row, and the
    first-pass record does not resolve native host breadth, exact profile-to-protein
    correspondence, direct cyclic-nucleotide substrate, exact NACHT-mediated activation
    route, phage target breadth, endogenous DS-8 activity, or whether DS-8 should
    be related to the broader NLR-like bNACHT system family.
  evidence:
  - reference: DOI:10.1126/science.adv7924
    snippet: To test for anti-phage defense, we placed each TU with its predicted
      native promoter region on a low-copy number plasmid in E. coli MG1655 and challenged
      these strains with a panel of 24 diverse E. coli phages (Fig. 3; fig. S2). In
      total, 42 (45% of 94) of the cloned TUs produced smaller plaque sizes or reduced
      the efficiency of plating (EOP) at least ten-fold relative to an empty vector
      control strain
    notes: DeWeirdt et al. validate predicted transcriptional units by measuring plaquing
      relative to an empty vector control strain.
  - reference: DOI:10.1126/science.adv7924
    snippet: First, we investigated DS-8, a single protein system containing a metallophosphatase
      domain (Fig. 5A) which is homologous to the human protein SMPDL3A, a phosphodiesterase
      that cleaves cGAMP to modulate cGAS-STING immunity signaling
    notes: DeWeirdt et al. identify DS-8 as single-protein.
  - reference: DOI:10.1126/science.adv7924
    snippet: Mutating either of two predicted catalytic residues in the metallophosphatase
      domain or a residue likely critical to NACHT ATPase activity completely ablated
      defense by DS-8, indicating that both domains and metallophosphatase activity
      are essential for protection
    notes: DeWeirdt et al. state that DS-8 metallophosphatase and NACHT catalytic
      mutants ablate defense.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S6.xlsx
    snippet: "MNAC\tNZ_RRWS01000004.1\tGCF_003892555.1\t-\tTrue\tFalse\tFalse\tTrue\t\
      DefensePredictor hits\t83803\t86847\tmetallophosphoesterase\tWP_032203427.1\t\
      9.394229333124514\t6.212606095751518\tTrue\tTrue\tPredicted novel defense gene\t\
      DS-8"
    notes: The final Science supplementary Table S6 maps working_id MNAC to DS_name
      DS-8, marks the cloned transcriptional unit as defensive, and records NZ_RRWS01000004.1
      positions 83803-86847 with product accession WP_032203427.1.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\t1.2\tpLAND\t24-03-08_EV_HHHD_PIN2_CRDO.png\t40000000\tMNAC\t24-03-08\t\
      24-03-08_MNAC_GHOS_BRNT_IMPD.png\t1\t10\tY\t100\t5.6020599913279625\tTrue\t\t\
      \tLB\t37"
    notes: The final Science supplementary Table S7 reports an MNAC assay row with
      a Bas1 phage readout and a -log(EOP) value of 5.602.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      3000000\tMNAC\tK375A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      6\t3\t\t3000000\t0"
    notes: The final Science supplementary Table S7 reports the MNAC K375A Bas1 mutant
      row with a -log(EOP) value of 0.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      3000000\tMNAC\tN84A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      6\t2\t\t2000000\t0.1760912591"
    notes: The final Science supplementary Table S7 reports the MNAC N84A Bas1 mutant
      row with a -log(EOP) value of 0.176.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S7.xlsx
    snippet: "Bas1\tA.1\tMG1655\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      3000000\tMNAC\tD52A\t24-07-10\t24-07-10_EV_MNAC-K375A_MNAC-N84A_MNAC-D52A.png\t\
      6\t4\t\t4000000\t-0.1249387366"
    notes: The final Science supplementary Table S7 reports the MNAC D52A Bas1 mutant
      row with a -log(EOP) value of -0.125.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "MNAC\tDS-8\tTrue"
    notes: The final Science supplementary Table S8 maps MNAC to replicated display
      name DS-8.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "MNAC\t1.0\t1014.0\tWP_032203427.1\tMetallophosphatase\t5KAR_A\tAcid\
      \ sphingomyelinase-like phosphodiesterase 3b; phosphoesterase, extracellular,\
      \ membrane\thhpred_8521728.hhr\t1.0\t275.0\t0.997\t2024-04-16 00:00:00"
    notes: The final Science supplementary Table S8 reports a metallophosphatase HHpred
      hit for WP_032203427.1 in MNAC.
  - reference: https://pmc-oa-opendata.s3.amazonaws.com/PMC13092281.1/NIHMS2163519-supplement-Table_S8.xlsx
    snippet: "MNAC\t1.0\t1014.0\tWP_032203427.1\tNACHT\t8FML_A\tBaculoviral IAP repeat-containing\
      \ protein 1e; Inflammasome, Innate immunity, Bacterial ligand, host-pathogen\
      \ interaction, Protein complex, IMMUNE SYSTEM\thhpred_8521728.hhr\t331.0\t734.0\t\
      1.0\t2024-04-16 00:00:00"
    notes: The final Science supplementary Table S8 reports a NACHT HHpred hit for
      WP_032203427.1 in MNAC.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/List_system_article.md
    snippet: '| DS-8 | 10\.1101/2025\.01\.08\.631726 | DefensePredictor: A machine
      learning model to discover novel prokaryotic immune systems | '
    notes: The pinned DefenseFinder article registry maps the DS-8 source key to the
      preprint DOI for the DeWeirdt et al. DefensePredictor study, which has since
      been published in Science.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/Liste_hmm_system.md
    snippet: '| DS-8__DS-8                                       |                                                  |
      DS-8                   | Custom                  | 200    |'
    notes: The pinned DefenseFinder HMM inventory records DS-8__DS-8 as a custom DS-8
      profile.
  - reference: https://raw.githubusercontent.com/mdmparis/defense-finder-models/afb0e5a8b466be53586b13266f5d38d98c3ac268/DefenseFinder_rules.tsv
    notes: The pinned DefenseFinder rules table does not list DS-8, leaving rule-level
      detection criteria unresolved.
  attaches_to:
  - causal_graphs#ds_8_locus_reduces_phage_plaquing
  posed_by: codex
  posed_date: '2026-09-28'
curation_history:
- timestamp: '2026-09-28T10:43:27Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Minted DS-8 system as a DOI-backed GENOMICS TraitRecord under phage defense
    system after an ignored-and-hidden duplicate review found no exact live TraitMech,
    METPO, history, or prior proposal record; kept the graph at cloned MNAC transcriptional-unit
    level because the pinned DefenseFinder DS-8 HMM row is not backed by a rules row;
    proposals/metpo_traitmech_v309 reserves the replacement placeholder.
  llm_assisted: true
- timestamp: '2026-09-28T10:43:28Z'
  curator: codex
  action: REVIEW_CANONICAL_EXAMPLE_EVIDENCE_GAP
  changes: Reviewed DS-8 system canonical_examples and left them empty because DeWeirdt
    et al. support cloned MNAC plaquing assays in E. coli MG1655 plus a DefenseFinder
    DS-8 model, but not a direct named native microbial isolate exemplar with experimentally
    verified endogenous DS-8 activity. No paid research was used.
  llm_assisted: true
- timestamp: '2026-09-28T11:24:51Z'
  curator: codex
  action: ADDRESS_REVIEW_FINDINGS
  changes: 'Addressed PR review issues #1397 and #1398 by replacing the ambiguous
    generic DS naming quote with DS-8-specific single-protein and catalytic-mutant
    article snippets, adding final Science Table S7 MNAC K375A/N84A/D52A Bas1 mutant
    evidence, and narrowing the open DS-8 knowledge gap to substrate identity, NACHT-mediated
    activation route, native-host and phage breadth, exact profile mapping, and DefenseFinder
    rule-level criteria.'
  llm_assisted: true