stlB

id: Q54FI3
gene_symbol: stlB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: StlB (Steely B, also called Steely2, PKS37 or dipks37) is a large
  (~2968-residue) multidomain hybrid biosynthetic enzyme of the social amoeba
  Dictyostelium discoideum. It fuses an N-terminal type I fatty-acid-synthase-like
  module (ketosynthase, acyltransferase/malonyl transacylase, dehydratase, enoyl
  reductase, ketoreductase and acyl-carrier-protein domains) to a C-terminal type
  III chalcone-synthase-like polyketide synthase domain, an architecture termed
  "steely" that is unique to dictyostelids. StlB synthesizes the acylphloroglucinol
  backbone (THPH/PCP, 2,4,6-trihydroxyphenyl-hexan-1-one) of DIF-1 by loading a
  hexanoyl starter, performing three malonyl-CoA polyketide extensions and a final
  intramolecular Claisen (C6-to-C1) cyclization. The THPH product is subsequently
  dichlorinated by the halogenase ChlA and O-methylated by the methyltransferase
  DmtA to yield DIF-1 (1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one),
  a chlorinated alkylphenone morphogen. Because StlB catalyzes the committed first
  step of DIF-1 biosynthesis, it is required, via DIF-1, for prestalk and stalk
  cell differentiation, formation of the basal disc and lower cup of the fruiting
  body, slug migration, and developmental (vacuolar) cell death. It is expressed
  during multicellular development, coordinately with dmtA.
existing_annotations:
- term:
    id: GO:0006633
    label: fatty acid biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic inference of fatty acid biosynthesis from type I FAS
      family members. StlB contains FAS-like catalytic domains but is a hybrid
      polyketide synthase whose physiological output is the acylphloroglucinol
      backbone of DIF-1, not free fatty acids.
    action: REMOVE
    reason: This IBA is an over-propagation from the metazoan type I FAS family.
      The N-terminal FAS-like module of StlB only generates a hexanoyl starter that
      is channeled internally to the C-terminal type III PKS domain to build a
      polyketide; StlB does not produce fatty acids as pathway products. Polyketide
      biosynthetic process and DIF-1 biosynthetic process capture the true biology.
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: PANTHER:PTN001711534
        source_label: "PANTHER node for the type I FAS / PKS family"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Fatty acid biosynthesis reflects canonical type I FAS members; StlB is a hybrid FAS-type III PKS that makes a polyketide (DIF-1 backbone), not fatty acids"
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: Steely proteins possess six catalytic domains homologous to
        metazoan type I fatty acid synthases (FASs)
    - reference_id: PMID:16906151
      supporting_text: this type III PKS efficiently synthesizes PCP
- term:
    id: GO:0004315
    label: 3-oxoacyl-[acyl-carrier-protein] synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO annotation from the ketoacyl synthase (KS) domain
      signature. StlB does contain a functional beta-ketoacyl synthase (condensing)
      domain used to elongate the acyl intermediate, so this is a genuine component
      activity, but it is not the distinctive core function of the protein.
    action: KEEP_AS_NON_CORE
    reason: The KS domain and its condensation (3-oxoacyl-ACP synthase) chemistry
      are real parts of the StlB catalytic cycle, but the enzyme's defining function
      is synthesis of the DIF-1 acylphloroglucinol backbone (THPH synthase). This
      domain-level activity is best kept as non-core supporting machinery.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: Steely proteins possess six catalytic domains homologous to
        metazoan type I fatty acid synthases (FASs)
- term:
    id: GO:0006633
    label: fatty acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO annotation from the ketoacyl synthase active-site
      signature. As with the IBA, this reflects FAS-like domains rather than the
      actual product of StlB, which is a polyketide (DIF-1 backbone).
    action: MARK_AS_OVER_ANNOTATED
    reason: The FAS-like domains of StlB build a hexanoyl intermediate that is fed
      into the type III PKS domain to make an acylphloroglucinol; the enzyme does
      not release fatty acids. Annotating fatty acid biosynthetic process
      over-states a housekeeping-lipid role that StlB does not play.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: the acylphloroglucinol skeleton of both DIF-1 and its in vivo
        degradation product DIF-3
- term:
    id: GO:0016210
    label: naringenin-chalcone synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation derived from the C-terminal type III
      (chalcone-synthase-like) PKS domain and its EC 2.3.1.74 mapping. The domain
      is homologous to plant chalcone synthase, but the demonstrated physiological
      product of StlB is an acylphloroglucinol (THPH), not naringenin chalcone.
    action: MODIFY
    reason: The type III PKS domain is CHS-like, but experimentally StlB (Steely2)
      synthesizes the acylphloroglucinol backbone (THPH/PCP) of DIF-1, not a
      chalcone. The more accurate molecular function is THPH synthase activity.
    proposed_replacement_terms:
    - id: GO:0106265
      label: THPH synthase activity
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: the acylphloroglucinol skeleton of both DIF-1 and its in vivo
        degradation product DIF-3
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO annotation from the enoyl reductase / ketoreductase
      domains. StlB contains ER and KR domains that perform reductive tailoring of
      the growing chain, so oxidoreductase activity is present but generic.
    action: KEEP_AS_NON_CORE
    reason: The ER and KR domains are genuine oxidoreductase modules within the
      FAS-like part of StlB, but this is a very general activity that reflects
      component chemistry rather than the enzyme's distinctive THPH-synthesizing
      function.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: Steely proteins possess six catalytic domains homologous to
        metazoan type I fatty acid synthases (FASs)
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Very high-level root transferase term propagated from InterPro. Not
      informative about the specific function of StlB.
    action: MARK_AS_OVER_ANNOTATED
    reason: transferase activity is an uninformative superclass. StlB has specific,
      better-characterized transferase/acyltransferase and synthase activities;
      the bare root term adds no curation value.
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO annotation from the acyltransferase (malonyl-CoA:ACP
      transacylase, MAT) domain. StlB has a functional AT/MAT domain that loads
      malonyl units, so acyltransferase activity is a real component activity.
    action: KEEP_AS_NON_CORE
    reason: The AT/MAT domain genuinely catalyzes acyl transfer during chain
      loading, but this is supporting machinery for the core THPH synthase
      function rather than a distinctive activity by itself.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: Steely proteins possess six catalytic domains homologous to
        metazoan type I fatty acid synthases (FASs)
- term:
    id: GO:0031177
    label: phosphopantetheine binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO annotation from the carrier (acyl-carrier-protein) domain.
      StlB contains a phosphopantetheine-attachment (carrier) domain that tethers
      the growing acyl/polyketide chain, so this cofactor-binding activity is
      correct but ancillary.
    action: KEEP_AS_NON_CORE
    reason: The ACP/carrier domain of StlB is post-translationally modified with
      phosphopantetheine and binds it covalently, consistent with this annotation.
      It is a genuine but accessory feature supporting substrate channeling rather
      than the enzyme's core synthase function.
- term:
    id: GO:0044550
    label: secondary metabolite biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning annotation. DIF-1 and related acylphloroglucinols
      are secondary metabolites, so this high-level process term is correct.
    action: ACCEPT
    reason: StlB produces the polyketide backbone of DIF-1, a bona fide secondary
      metabolite, so involvement in secondary metabolite biosynthetic process is
      accurate, if more general than polyketide/DIF-1 biosynthetic process.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: responsible for biosynthesis of the DIF acylphloroglucinol
        scaffold
- term:
    id: GO:0106265
    label: THPH synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Rhea-based electronic annotation of THPH synthase activity (hexanoyl-CoA
      + 3 malonyl-CoA -> 2,4,6-trihydroxyphenylhexan-1-one). This is the
      experimentally demonstrated core activity of StlB.
    action: ACCEPT
    reason: THPH synthase activity is exactly the reaction StlB (Steely2) was shown
      to catalyze, producing the acylphloroglucinol precursor of DIF-1. The
      electronic Rhea annotation agrees with the experimental evidence.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: this type III PKS efficiently synthesizes PCP
- term:
    id: GO:0009813
    label: flavonoid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway-based electronic annotation propagated from the chalcone
      synthase EC 2.3.1.74 mapping to the plant flavonoid pathway. Dictyostelium
      does not make flavonoids; StlB makes the DIF-1 acylphloroglucinol backbone.
    action: REMOVE
    reason: Flavonoid biosynthesis is a plant-specific pathway. This annotation is
      an artifact of mapping the CHS-like domain / EC 2.3.1.74 onto the flavonoid
      UniPathway. StlB has no role in flavonoid biosynthesis in the amoeba; its
      product feeds DIF-1 (secondary metabolite / polyketide) biosynthesis.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: the acylphloroglucinol skeleton of both DIF-1 and its in vivo
        degradation product DIF-3
- term:
    id: GO:0016210
    label: naringenin-chalcone synthase activity
  evidence_type: EXP
  original_reference_id: PMID:16906151
  qualifier: enables
  review:
    summary: Experimental annotation based on the CHS-like C-terminal type III PKS
      domain assayed in vitro. Although the domain is homologous to chalcone
      synthase (EC 2.3.1.74) and can act as an iterative type III PKS, the product
      demonstrated for StlB is an acylphloroglucinol (THPH/PCP), not naringenin
      chalcone.
    action: MODIFY
    reason: The demonstrated reaction is synthesis of the acylphloroglucinol
      skeleton of DIF-1 via three polyketide extensions and a Claisen cyclization,
      captured precisely by THPH synthase activity. naringenin-chalcone synthase
      names a specific plant reaction the enzyme does not physiologically perform,
      so the term should be updated to the demonstrated activity.
    proposed_replacement_terms:
    - id: GO:0106265
      label: THPH synthase activity
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: the acylphloroglucinol skeleton of both DIF-1 and its in vivo
        degradation product DIF-3
- term:
    id: GO:0106265
    label: THPH synthase activity
  evidence_type: EXP
  original_reference_id: PMID:16906151
  qualifier: enables
  review:
    summary: Experimental demonstration that the StlB (Steely2) C-terminal type III
      PKS synthesizes PCP/THPH, the acylphloroglucinol skeleton of DIF-1, via three
      polyketide extensions of a hexanoyl starter and a CHS-like intramolecular
      Claisen condensation. This is the defining molecular function of StlB.
    action: ACCEPT
    reason: In vitro assays of the isolated C-terminal domain and in vivo knockout
      plus PCP rescue directly establish StlB as the THPH/PCP synthase of the DIF-1
      pathway. This is the core activity.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: this type III PKS efficiently synthesizes PCP
    - reference_id: PMID:16906151
      supporting_text: confirms Steely2-mediated catalysis of PCP biosynthesis in
        vivo
- term:
    id: GO:0018893
    label: dibenzofuran metabolic process
  evidence_type: IMP
  original_reference_id: PMID:36252029
  qualifier: involved_in
  review:
    summary: This term appears to be a chemical mis-mapping. DIF-1 is a chlorinated
      acylphloroglucinol (an alkylphenone), not a dibenzofuran, and the cited paper
      is about the pks5-derived dictyodenes and mentions StlB only as being required
      for DIF-1 synthesis. The intended biology is StlB's role in producing the
      DIF-1 polyketide.
    action: MODIFY
    reason: dibenzofuran metabolic process is chemically inappropriate for the DIF-1
      acylphloroglucinol product of StlB, and PMID:36252029 does not characterize
      dibenzofuran metabolism by StlB. The supported biology, that StlB is required
      for DIF-1 synthesis, is better represented by DIF-1 biosynthetic process.
    proposed_replacement_terms:
    - id: GO:0031148
      label: DIF-1 biosynthetic process
    supported_by:
    - reference_id: PMID:36252029
      supporting_text: StlB is required for the synthesis of differentiation-inducing
        factor I
- term:
    id: GO:0031149
    label: sorocarp stalk cell differentiation
  evidence_type: IGI
  original_reference_id: PMID:24096661
  qualifier: involved_in
  review:
    summary: Genetic-interaction evidence (with stlA) that Steely polyketides drive
      prestalk/stalk differentiation. DIF-1, the product of the StlB pathway, is the
      major stalk cell inducer, and the stlA/stlB double knockout loses pstA marker
      expression.
    action: ACCEPT
    reason: Loss of Steely-derived polyketides (including DIF-1 from StlB) impairs
      prestalk/stalk cell differentiation, supporting involvement in sorocarp stalk
      cell differentiation. This is a genuine developmental role of StlB acting
      through DIF-1.
    supported_by:
    - reference_id: PMID:24096661
      supporting_text: a product of SteelyB, was identified as the major stalk cell
        inducer
    - reference_id: PMID:24096661
      supporting_text: the stlA and stlB double-knockout mutant lost pstA marker gene
        expression
- term:
    id: GO:0048102
    label: autophagic cell death
  evidence_type: IMP
  original_reference_id: PMID:25518941
  qualifier: acts_upstream_of_or_within
  review:
    summary: stlB disruption (and cerulenin inhibition of polyketide synthesis)
      almost completely prevents c-di-GMP-induced vacuolar cell death, showing that
      an stlB-dependent polyketide (DIF-1) is required for this developmental cell
      death. StlB acts upstream via DIF-1 rather than directly executing cell death.
    action: KEEP_AS_NON_CORE
    reason: The requirement for StlB in developmental (vacuolar/autophagic) cell
      death is an indirect, downstream consequence of DIF-1 production, not a core
      molecular function of the enzyme. It is a valid acts_upstream_of_or_within
      annotation but non-core.
    supported_by:
    - reference_id: PMID:25518941
      supporting_text: the stlB-initiated biosynthetic cascade included at least one
        polyketide required for the major part of cell death induction by c-di-GMP
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IGI
  original_reference_id: PMID:27305283
  qualifier: acts_upstream_of_or_within
  review:
    summary: DIF-1, produced via StlB, induces prestalk gene expression; in the
      stlA/stlB double knockout, prestalk gene expression is reduced. StlB thereby
      acts upstream of positive regulation of prestalk gene expression.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream, DIF-1-mediated transcriptional effect rather than
      a core molecular function of StlB. The generic term is a valid
      acts_upstream_of_or_within annotation but is non-core.
    supported_by:
    - reference_id: PMID:27305283
      supporting_text: expression of prestalk genes is also reduced
    - reference_id: PMID:18402932
      supporting_text: induces the expression of a subset of prestalk genes
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IGI
  original_reference_id: PMID:27305283
  qualifier: acts_upstream_of_or_within
  review:
    summary: DIF-1, produced via StlB, represses prespore gene expression, so StlB
      acts upstream of negative regulation of gene expression through its DIF-1
      product.
    action: KEEP_AS_NON_CORE
    reason: Repression of prespore genes is a downstream, DIF-1-mediated
      transcriptional effect, not a core molecular function of StlB. Valid as an
      acts_upstream_of_or_within annotation but non-core.
    supported_by:
    - reference_id: PMID:18402932
      supporting_text: represses the expression of all tested prespore genes
- term:
    id: GO:0031149
    label: sorocarp stalk cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:18402932
  qualifier: acts_upstream_of_or_within
  review:
    summary: The stlB (PKS) null mutant, which makes no DIF-1, has ~35% fewer
      prestalk cells and a specific deficit of prestalk-O cells and anterior-like
      cells, with rescue by exogenous DIF-1. StlB is required, via DIF-1, for
      prestalk/stalk cell differentiation.
    action: ACCEPT
    reason: Direct mutant phenotype shows StlB (through DIF-1) is needed for normal
      prestalk/stalk cell differentiation, supporting this annotation.
    supported_by:
    - reference_id: PMID:18402932
      supporting_text: Both methyltransferase null and PKS null mutants produced only
        approximately 65% of the wild-type proportion of prestalk cells
    - reference_id: PMID:18402932
      supporting_text: The backbone of DIF-1 consists of a 12-carbon polyketide
        produced by the steely B (stlB) PKS
- term:
    id: GO:0031288
    label: sorocarp morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:18402932
  qualifier: acts_upstream_of_or_within
  review:
    summary: The stlB null mutant forms strikingly abnormal fruiting bodies lacking
      the basal disc, with a rudimentary lower cup and a spore mass that slips down
      the stalk; these defects are corrected by DIF-1. StlB is required, via DIF-1,
      for normal sorocarp morphogenesis.
    action: KEEP_AS_NON_CORE
    reason: The morphogenesis defects are downstream developmental consequences of
      losing DIF-1, an indirect role of the enzyme. It is a valid
      acts_upstream_of_or_within annotation but non-core relative to the molecular
      synthase function.
    supported_by:
    - reference_id: PMID:18402932
      supporting_text: The basal disc is almost entirely absent from the PKS null
        mutant fruiting bodies
    - reference_id: PMID:18402932
      supporting_text: DIF-1 is required for slug migration and crucially for the
        formation of the lower cup and basal disc of the fruiting body
- term:
    id: GO:0030639
    label: polyketide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16906151
  qualifier: involved_in
  review:
    summary: Direct assay evidence that StlB is an iterative polyketide synthase
      producing the acylphloroglucinol (PCP/THPH) polyketide. This is a core
      biological process for StlB.
    action: ACCEPT
    reason: In vitro and in vivo evidence establishes StlB as a polyketide synthase
      building the DIF-1 acylphloroglucinol backbone, directly supporting
      involvement in polyketide biosynthetic process.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: this type III PKS efficiently synthesizes PCP
- term:
    id: GO:0031148
    label: DIF-1 biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:16906151
  qualifier: acts_upstream_of_or_within
  review:
    summary: StlB (Steely2) is the missing DIF-pathway PCP synthase; the Steely2
      null fails to accumulate DIF-1 and is rescued by exogenous PCP, identifying
      StlB as catalyzing the committed first step of DIF-1 biosynthesis. This is a
      core biological process for StlB.
    action: ACCEPT
    reason: Genetic and biochemical evidence directly place StlB at the start of the
      DIF-1 biosynthetic pathway, producing the acylphloroglucinol scaffold that is
      then chlorinated and methylated to DIF-1.
    supported_by:
    - reference_id: PMID:16906151
      supporting_text: our definitive identification of Steely2 as the missing
        DIF-pathway PCP synthase (DAPS)
    - reference_id: PMID:16906151
      supporting_text: confirms Steely2-mediated catalysis of PCP biosynthesis in
        vivo
core_functions:
- description: StlB is a hybrid type I FAS / type III PKS ("steely") enzyme that
    synthesizes the acylphloroglucinol backbone (THPH/PCP) of DIF-1. Its N-terminal
    FAS-like module supplies a hexanoyl acyl intermediate that the C-terminal
    CHS-like type III PKS domain extends with three malonyl units and cyclizes,
    catalyzing the committed first step of DIF-1 biosynthesis.
  molecular_function:
    id: GO:0106265
    label: THPH synthase activity
  directly_involved_in:
  - id: GO:0031148
    label: DIF-1 biosynthetic process
  - id: GO:0030639
    label: polyketide biosynthetic process
  supported_by:
  - reference_id: PMID:16906151
    supporting_text: this type III PKS efficiently synthesizes PCP
  - reference_id: PMID:16906151
    supporting_text: our definitive identification of Steely2 as the missing
      DIF-pathway PCP synthase (DAPS)
  - reference_id: PMID:16906151
    supporting_text: responsible for biosynthesis of the DIF acylphloroglucinol
      scaffold
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16906151
  title: Biosynthesis of Dictyostelium discoideum differentiation-inducing factor
    by a hybrid type I fatty acid-type III polyketide synthase.
  findings:
  - statement: StlB (Steely2) is a hybrid enzyme with six type I FAS-like catalytic
      domains fused to a C-terminal iterative type III (chalcone-synthase-like) PKS
      domain.
    supporting_text: Steely proteins possess six catalytic domains homologous to
      metazoan type I fatty acid synthases (FASs) but feature an iterative type III
      polyketide synthase (PKS)
  - statement: The StlB type III PKS domain synthesizes PCP, the acylphloroglucinol
      skeleton of DIF-1 and its degradation product DIF-3.
    supporting_text: this type III PKS efficiently synthesizes PCP
  - statement: StlB is the DIF-pathway PCP (THPH) synthase; the Steely2 knockout
      does not accumulate DIF-1 and is rescued by exogenous PCP.
    supporting_text: confirms Steely2-mediated catalysis of PCP biosynthesis in vivo
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Primary paper establishing StlB (Steely2) as the DIF-1 pathway
      acylphloroglucinol (THPH/PCP) synthase by combined in vitro enzymology and in
      vivo knockout/rescue; PMID and title verified against the cached record."
- id: PMID:18402932
  title: DIF-1 induces the basal disc of the Dictyostelium fruiting body.
  findings:
  - statement: The stlB (PKS) null mutant makes no DIF-1 and produces long, thin
      slugs, ~35% fewer prestalk cells, and fruiting bodies lacking the basal disc
      and a proper lower cup; defects are rescued by exogenous DIF-1.
    supporting_text: DIF-1 is required for slug migration and crucially for the
      formation of the lower cup and basal disc of the fruiting body
  - statement: The DIF-1 backbone is a 12-carbon polyketide made by the steely B
      (stlB) PKS.
    supporting_text: The backbone of DIF-1 consists of a 12-carbon polyketide
      produced by the steely B (stlB) PKS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Full-text mutant-phenotype study directly establishing the
      developmental roles (prestalk differentiation, basal disc / lower cup) that
      require StlB-dependent DIF-1."
- id: PMID:24096661
  title: Steely enzymes are involved in prestalk and prespore pattern formation.
  findings:
  - statement: DIF-1 (product of SteelyB/StlB) is the major stalk cell inducer, and
      the stlA/stlB double knockout loses pstA marker gene expression.
    supporting_text: the stlA and stlB double-knockout mutant lost pstA marker gene
      expression
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Abstract-only in the cache; supports the prestalk/pattern-formation
      role of Steely polyketides including DIF-1 from StlB."
- id: PMID:25518941
  title: c-di-GMP induction of Dictyostelium cell death requires the polyketide DIF-1.
  findings:
  - statement: stlB disruption almost completely prevents c-di-GMP-induced vacuolar
      cell death, showing an stlB-dependent polyketide (DIF-1) is required.
    supporting_text: the stlB-initiated biosynthetic cascade included at least one
      polyketide required for the major part of cell death induction by c-di-GMP
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Full-text study; StlB contributes indirectly (via DIF-1) to
      developmental cell death."
- id: PMID:27305283
  title: Stalk cell differentiation without polyketides in the cellular slime mold.
  findings:
  - statement: In the stlA/stlB double knockout most pstA cells are lost and prestalk
      gene expression is reduced.
    supporting_text: expression of prestalk genes is also reduced
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Abstract-only in the cache; supports StlB (via DIF-1) acting
      upstream of prestalk gene expression."
- id: PMID:36252029
  title: Yellow polyketide pigment suppresses premature hatching in social amoeba.
  findings:
  - statement: The paper characterizes pks5-derived dictyodenes and mentions StlB
      only as required for DIF-1 synthesis.
    supporting_text: StlB is required for the synthesis of differentiation-inducing
      factor I
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: "This paper is about PKS5/dictyodenes and does not characterize
      dibenzofuran metabolism by StlB; it references StlB only for DIF-1 synthesis.
      It does not support the dibenzofuran metabolic process annotation."