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myxochelin A

naturalproductmech:mibig-b9324089ad MINTED SEEDED

Grounding review: No 3-star ChEBI entry shares this structure, so the record keeps a content-hashed identifier.
What these status tags mean

Curation status describes a workflow state. SEEDED means the record entered through the source-seeding workflow; it does not imply that no later curation occurred. PROPOSED marks an addition awaiting review; REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record. These are workflow decisions, not independently verified human review. Agent-assisted contributions may appear in the record history.

Grounding describes the identifier mapping: EXACT uses an ontology identity asserted by the source; MINTED keeps a local identifier when no defensible ontology identity is available; REVIEW_NEEDED flags an exact structure whose ontology identity needs adjudication. The grounding note retains any unresolved alternatives. These tags do not establish the strength of producer or activity evidence.

Structure

Standard InChIKeyWNBVGSNESTZACV-LBPRGKRZSA-N
SMILESOC[C@H](CCCCNC(=O)C1=CC=CC(O)=C1O)NC(=O)C1=CC=CC(O)=C1O
Stereochemistryfully defined
Cross-referencesnpatlas:NPA02219, pubchem:16093504, npatlas:NPA002219

Filing pathway

Alkaloids — computed by NPClassifier npclassifier.gnps2.org@2026-09-07, which is why it is pinned rather than recomputed. The gene cluster's asserted class is nrps, pks, from MIBiG.

Producer organisms 4

A claim that this taxon makes the compound. The basis says what the evidence addressed — a knockout and a database assertion are not the same claim.

TaxonBasisClusterEvidence
Stigmatella aurantiaca Sg a15
NCBITaxon:675526		 SOURCE_ASSERTION mibig:BGC0001345 PMID:11562468
Archangium violaceum
NCBITaxon:83451		 SOURCE_ASSERTION mibig:BGC0002324 PMID:34623817
Pseudoalteromonas piscicida
NCBITaxon:43662		 SOURCE_ASSERTION mibig:BGC0002491 PMID:30217842
Myxococcus xanthus DK 1622
NCBITaxon:246197		 SOURCE_ASSERTION mibig:BGC0002492 PMID:30217842

Occurrences 3

Somebody found the compound in this organism and cited it. That is not a claim that the organism makes it, and nothing here promotes one to the other.

TaxonSourceReference
Streptomyces albus
NCBITaxon:1888		 LOTUS DOI:10.1093/FEMSLE/FNX155
Angiococcus disciformis
NCBITaxon:38		 LOTUS DOI:10.7164/ANTIBIOTICS.42.14
Stigmatella aurantiaca
NCBITaxon:41		 LOTUS DOI:10.1073/PNAS.201167098

Biosynthetic gene clusters 4

AccessionHostLocus evidenceGenome
mibig:BGC0001345 Stigmatella aurantiaca Sg a15
NCBITaxon:675526 		CLUSTER_DEMONSTRATED genbank:AF299336.1
mibig:BGC0002324 Archangium violaceum
NCBITaxon:83451 		CLUSTER_UNSTATED genbank:CP069338.1
mibig:BGC0002491 Pseudoalteromonas piscicida
NCBITaxon:43662 		CLUSTER_DEMONSTRATED genbank:JXXW01000072.1
mibig:BGC0002492 Myxococcus xanthus DK 1622
NCBITaxon:246197 		CLUSTER_DEMONSTRATED genbank:CP000113.1

A locus claim and a taxon claim are different questions. Heterologous expression settles the first and leaves the second where the isolation report left it.

Biosynthesis curated

Written by a curator with claim-level evidence on each step; not derived from a source. This is what the rest of the record exists to support.

StepEnzymeReactionSubstrate → productEvidence
1 MxcE 2,3-DHBA-AMP ligase
UniProtKB:Q9F638		 ungrounded → ungrounded DOI:10.1073/pnas.201167098
2 MxcF isochorismatase and aryl carrier protein
UniProtKB:Q9F637		 ungrounded → ungrounded DOI:10.1073/pnas.201167098
3 MxcG peptide synthetase with reductase domain
UniProtKB:Q9F636		 ungrounded → ungrounded DOI:10.1073/pnas.201167098

Step 1: MxcE adenylates 2,3-dihydroxybenzoic acid for transfer to the MxcF aryl carrier protein; the carrier-protein thioester is left ungrounded as a pathway intermediate.

Step 2: MxcF supplies the aryl carrier protein that receives activated 2,3-DHBA from MxcE and presents it to MxcG; its isochorismatase module contributes to DHBA formation from chorismate.

Step 3: MxcG adenylates lysine, condenses two MxcF-delivered DHBA groups with lysine, and uses its reductase domain to release the myxochelin A alcohol.

Mechanism & Biosynthesis Overview

PRODUCERS & OCCURRENCE 4 producers (0 causal) 3 cited occurrences BIOSYNTHETIC LOCUS 4 gene clusters 3 curated pathway steps NATURAL PRODUCT myxochelin A naturalproductmech:mibig-b9324089ad Alkaloids TARGETS & BIOACTIVITY 0 molecular targets 1 bioactivity · 3 graphs

Causal graph — bioactivity 2 nodes, 1 edge

Myxochelin A inhibits human 5-lipoxygenase in a 5-LO activity assay.

SubjectPredicateObjectNotesEvidence
myxochelin A inhibits human 5-lipoxygenase PubChem BioAssay AID 1801607 maps the 1.715 uM IC50 myxochelin A 5-LO activity assay to UniProtKB:P09917, the human ALOX5 protein.
DOI:10.1002/cbic.201500446
  • reference
    DOI:10.1002/cbic.201500446
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Schieferdecker et al. tested the myxochelin family against human 5-lipoxygenase; the BindingDB-deposited PubChem assay reports myxochelin A with IC50 1.715 uM.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Causal graph — biosynthesis 6 nodes, 5 edges

Partial Stigmatella aurantiaca myxochelin A assembly graph for the MxcE/MxcF/MxcG nonribosomal peptide synthetase machinery.

SubjectPredicateObjectNotesEvidence
2,3-dihydroxybenzoic acid is adenylated by MxcE MxcE adenylates DHBA before MxcF carrier-protein loading.
DOI:10.1073/pnas.201167098
https://www.uniprot.org/uniprotkb/Q9F638
  • reference
    DOI:10.1073/pnas.201167098
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Gaitatzis et al. expressed active MxcE, MxcF, and MxcG and reconstituted ATP-, lysine-, DHBA-, and NAD(P)H-dependent myxochelin A formation in vitro.
  • reference
    https://www.uniprot.org/uniprotkb/Q9F638
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-09-27
    notes
    UniProtKB:Q9F638 resolves to the AF299336.1 mxcE gene product used for the Stigmatella myxochelin pathway.
MxcE loads activated 2,3-DHBA onto MxcF The MxcF aryl carrier protein receives activated DHBA for delivery to MxcG.
DOI:10.1073/pnas.201167098
https://www.uniprot.org/uniprotkb/Q9F637
  • reference
    DOI:10.1073/pnas.201167098
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Gaitatzis et al. expressed active MxcE, MxcF, and MxcG and reconstituted ATP-, lysine-, DHBA-, and NAD(P)H-dependent myxochelin A formation in vitro.
  • reference
    https://www.uniprot.org/uniprotkb/Q9F637
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-09-27
    notes
    UniProtKB:Q9F637 resolves to the AF299336.1 mxcF gene product used for the Stigmatella myxochelin pathway.
L-lysine is adenylated by MxcG The adenylation domain of MxcG activates lysine.
DOI:10.1073/pnas.201167098
https://www.uniprot.org/uniprotkb/Q9F636
  • reference
    DOI:10.1073/pnas.201167098
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Gaitatzis et al. expressed active MxcE, MxcF, and MxcG and reconstituted ATP-, lysine-, DHBA-, and NAD(P)H-dependent myxochelin A formation in vitro.
  • reference
    https://www.uniprot.org/uniprotkb/Q9F636
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-09-27
    notes
    UniProtKB:Q9F636 resolves to the AF299336.1 mxcG gene product used for the Stigmatella myxochelin pathway.
MxcF delivers activated 2,3-DHBA to MxcG MxcG condenses two MxcF-delivered DHBA units with the two amino groups of lysine.
DOI:10.1073/pnas.201167098
https://www.uniprot.org/uniprotkb/Q9F636
  • reference
    DOI:10.1073/pnas.201167098
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Gaitatzis et al. expressed active MxcE, MxcF, and MxcG and reconstituted ATP-, lysine-, DHBA-, and NAD(P)H-dependent myxochelin A formation in vitro.
  • reference
    https://www.uniprot.org/uniprotkb/Q9F636
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-09-27
    notes
    UniProtKB:Q9F636 resolves to the AF299336.1 mxcG gene product used for the Stigmatella myxochelin pathway.
MxcG reductively releases myxochelin A The C-terminal reductase domain of MxcG releases the PCP-bound thioester through aldehyde reduction to the myxochelin A alcohol.
DOI:10.1073/pnas.201167098
https://www.uniprot.org/uniprotkb/Q9F636
  • reference
    DOI:10.1073/pnas.201167098
    evidence type
    PRIMARY_EXPERIMENT
    notes
    Gaitatzis et al. expressed active MxcE, MxcF, and MxcG and reconstituted ATP-, lysine-, DHBA-, and NAD(P)H-dependent myxochelin A formation in vitro.
  • reference
    https://www.uniprot.org/uniprotkb/Q9F636
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-09-27
    notes
    UniProtKB:Q9F636 resolves to the AF299336.1 mxcG gene product used for the Stigmatella myxochelin pathway.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Causal graph — biosynthesis 7 nodes, 6 edges

Partial, explicitly proposed protein assignments for environmental clone m9-20, experimentally associated with a reported myxochelin A readout in an engineered S. albus J1074 reporter. Four exact deposited protein references are grounded; their individual catalytic functions are inferred, not assayed. The product readout is deliberately not grounded to this stereospecific owner. ASV47082.1/ASV47083.1 (MxcF-related), ASV47086.1 (PPTase), and proposed host PhzD compensation are not assigned myxochelin-specific functions here. Keep separate from the existing Stigmatella MxcE/F/G pathway.

SubjectPredicateObjectNotesEvidence
m9-20 MxcC-like reference protein is proposed to supply DHBA for m9-20-dependent biosynthesis in engineered S. albus J1074 Inferred role of the deposited MxcC-like homolog, not an individual enzyme assay, deletion, essentiality result or demonstrated physical interaction. Figure 4C homology and gene order, checked against reference-locus AF299336.1 protein alignments, support this assignment. The experiment introduced the complete cosmid into the engineered S. albus J1074 reporter, not this protein alone. These are environmental-clone reference sequences, not the existing Stigmatella UniProt proteins or verified expressed constructs. Exact product stereochemistry remains unassigned; see curator-m920-protein-and-product-scope.
DOI:10.1093/femsle/fnx155
https://www.ncbi.nlm.nih.gov/protein/ASV47079.1
https://rest.uniprot.org/uniparc/UPI000F0C4DE6.json
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    CURATOR_INFERENCE
    notes
    Figures 4C-E compare the m9-20 cluster with the Stigmatella mxc cluster and propose myxochelin biosynthesis. Individual m9-20 catalytic activities were not tested in the inspected main text. The supplement was not inspected and is not used as evidence.
  • reference
    https://www.ncbi.nlm.nih.gov/protein/ASV47079.1
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-10-11
    snippet
    2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase
    notes
    GenPept ASV47079.1: 263 aa, coded by KY560365.1:8829..9620; annotated 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase. The sequence exactly matches both the deposited CDS translation and its independent genetic-code-11 translation. Source: uncultured bacterium, taxon 77133, clone m9-20, Texas desert soil. This validates the reference identity, not the catalytic assignment.
  • reference
    https://rest.uniprot.org/uniparc/UPI000F0C4DE6.json
    evidence type
    DATABASE_ASSERTION
    notes
    UniParc UPI000F0C4DE6 (263 aa) links active EMBL ASV47079.1 (uncultured bacterium, taxon 77133) and inactive UniProtKB/TrEMBL A0A3G1J153, with zero active UniProtKB cross-references.
    retrieved on
    2026-10-30
m9-20 MxcD-like reference protein is proposed to supply DHBA for m9-20-dependent biosynthesis in engineered S. albus J1074 Inferred role of the deposited MxcD-like homolog, not an individual enzyme assay, deletion, essentiality result or demonstrated physical interaction. Figure 4C homology and gene order, checked against reference-locus AF299336.1 protein alignments, support this assignment. The experiment introduced the complete cosmid into the engineered S. albus J1074 reporter, not this protein alone. These are environmental-clone reference sequences, not the existing Stigmatella UniProt proteins or verified expressed constructs. Exact product stereochemistry remains unassigned; see curator-m920-protein-and-product-scope.
DOI:10.1093/femsle/fnx155
https://www.ncbi.nlm.nih.gov/protein/ASV47080.1
https://rest.uniprot.org/uniparc/UPI000F0CACEF.json
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    CURATOR_INFERENCE
    notes
    Figures 4C-E compare the m9-20 cluster with the Stigmatella mxc cluster and propose myxochelin biosynthesis. Individual m9-20 catalytic activities were not tested in the inspected main text. The supplement was not inspected and is not used as evidence.
  • reference
    https://www.ncbi.nlm.nih.gov/protein/ASV47080.1
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-10-11
    snippet
    isochorismate synthase
    notes
    GenPept ASV47080.1: 388 aa, coded by KY560365.1:9667..10833; annotated isochorismate synthase. The sequence exactly matches both the deposited CDS translation and its independent genetic-code-11 translation. Source: uncultured bacterium, taxon 77133, clone m9-20, Texas desert soil. This validates the reference identity, not the catalytic assignment.
  • reference
    https://rest.uniprot.org/uniparc/UPI000F0CACEF.json
    evidence type
    DATABASE_ASSERTION
    notes
    UniParc UPI000F0CACEF (388 aa) links active EMBL ASV47080.1 (uncultured bacterium, taxon 77133) and inactive UniProtKB/TrEMBL A0A3G1J168, with zero active UniProtKB cross-references.
    retrieved on
    2026-10-30
m9-20 MxcE-like reference protein is proposed to activate DHBA for m9-20-dependent biosynthesis in engineered S. albus J1074 Inferred role of the deposited MxcE-like homolog, not an individual enzyme assay, deletion, essentiality result or demonstrated physical interaction. Figure 4C homology and gene order, checked against reference-locus AF299336.1 protein alignments, support this assignment. The experiment introduced the complete cosmid into the engineered S. albus J1074 reporter, not this protein alone. These are environmental-clone reference sequences, not the existing Stigmatella UniProt proteins or verified expressed constructs. Exact product stereochemistry remains unassigned; see curator-m920-protein-and-product-scope.
DOI:10.1093/femsle/fnx155
https://www.ncbi.nlm.nih.gov/protein/ASV47081.1
https://rest.uniprot.org/uniparc/UPI000F0C0434.json
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    CURATOR_INFERENCE
    notes
    Figures 4C-E compare the m9-20 cluster with the Stigmatella mxc cluster and propose myxochelin biosynthesis. Individual m9-20 catalytic activities were not tested in the inspected main text. The supplement was not inspected and is not used as evidence.
  • reference
    https://www.ncbi.nlm.nih.gov/protein/ASV47081.1
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-10-11
    snippet
    enterobactin synthase subunit E
    notes
    GenPept ASV47081.1: 540 aa, coded by KY560365.1:10830..12452; annotated enterobactin synthase subunit E. The sequence exactly matches both the deposited CDS translation and its independent genetic-code-11 translation. Source: uncultured bacterium, taxon 77133, clone m9-20, Texas desert soil. This validates the reference identity, not the catalytic assignment.
  • reference
    https://rest.uniprot.org/uniparc/UPI000F0C0434.json
    evidence type
    DATABASE_ASSERTION
    notes
    UniParc UPI000F0C0434 (540 aa) links active EMBL ASV47081.1 (uncultured bacterium, taxon 77133) and inactive UniProtKB/TrEMBL A0A3G1J158, with zero active UniProtKB cross-references.
    retrieved on
    2026-10-30
m9-20 MxcG-like reference protein is proposed to assemble lysine and DHBA during m9-20-dependent biosynthesis in engineered S. albus J1074 Inferred role of the deposited MxcG-like homolog, not an individual enzyme assay, deletion, essentiality result or demonstrated physical interaction. Figure 4C homology and gene order, checked against reference-locus AF299336.1 protein alignments, support this assignment. The experiment introduced the complete cosmid into the engineered S. albus J1074 reporter, not this protein alone. These are environmental-clone reference sequences, not the existing Stigmatella UniProt proteins or verified expressed constructs. Exact product stereochemistry remains unassigned; see curator-m920-protein-and-product-scope.
DOI:10.1093/femsle/fnx155
https://www.ncbi.nlm.nih.gov/protein/ASV47084.1
https://rest.uniprot.org/uniparc/UPI000F0C6D63.json
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    CURATOR_INFERENCE
    notes
    Figures 4C-E compare the m9-20 cluster with the Stigmatella mxc cluster and propose myxochelin biosynthesis. Individual m9-20 catalytic activities were not tested in the inspected main text. The supplement was not inspected and is not used as evidence.
  • reference
    https://www.ncbi.nlm.nih.gov/protein/ASV47084.1
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-10-11
    snippet
    non-ribosomal peptide synthetase
    notes
    GenPept ASV47084.1: 1387 aa, coded by KY560365.1:13299..17462; annotated non-ribosomal peptide synthetase. The sequence exactly matches both the deposited CDS translation and its independent genetic-code-11 translation. Source: uncultured bacterium, taxon 77133, clone m9-20, Texas desert soil. This validates the reference identity, not the catalytic assignment.
  • reference
    https://rest.uniprot.org/uniparc/UPI000F0C6D63.json
    evidence type
    DATABASE_ASSERTION
    notes
    UniParc UPI000F0C6D63 (1387 aa) links active EMBL ASV47084.1 (uncultured bacterium, taxon 77133) and inactive UniProtKB/TrEMBL A0A3G1J160, with zero active UniProtKB cross-references.
    retrieved on
    2026-10-30
environmental clone m9-20 (KY560365.1) supports biosynthesis in the engineered reporter host m9-20-dependent biosynthesis in engineered S. albus J1074 Whole-clone heterologous-expression result in S. albus J1074::bpsA with the Sfp-type PPTase deleted. The clone-specific metabolite was absent from the empty-vector control. This does not assign a native donor species, make the host a native producer, or establish that each listed protein is necessary or sufficient. No physical complex is inferred.
DOI:10.1093/femsle/fnx155
https://www.ncbi.nlm.nih.gov/nuccore/KY560365.1
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    PRIMARY_EXPERIMENT
    snippet
    a single, clone-specific peak
    notes
    Main-text results and Figure 4A report a clone-specific peak from m9-20 culture extracts. The tested unit was the complete cosmid.
  • reference
    https://www.ncbi.nlm.nih.gov/nuccore/KY560365.1
    evidence type
    DATABASE_ASSERTION
    retrieved on
    2026-10-11
    notes
    KY560365.1 is the 27,396-nt m9-20 environmental insert; its reference cites PMID:28817927. The deposited source is an uncultured bacterium, not Streptomyces sp. FxanaC1 or the expression host.
m9-20-dependent biosynthesis in engineered S. albus J1074 produces a metabolite reported as reported myxochelin A (absolute configuration unverified) Reported identification by HRMS and co-elution with a purified myxochelin A standard: measured [M+H]+ 405.1657 versus calculated 405.1656 for C20H24N2O7. The inspected methods describe C18 co-injection, not a chiral separation; Figure 4B does not specify stereochemistry. Standard provenance and the supporting Figure S4 were not independently inspected. The readout therefore has no exact-structure identifier: this edge does not prove the S-configured owner or its opposite enantiomer, and reports no stereochemical contradiction.
DOI:10.1093/femsle/fnx155
  • reference
    DOI:10.1093/femsle/fnx155
    evidence type
    PRIMARY_EXPERIMENT
    snippet
    HRMS analysis of the clone-specific peak
    notes
    Main-text results, analytical methods and Figure 4 identify the clone-dependent peak as myxochelin A. The supplementary co-elution figure is cited by the authors but was not inspected.

Every edge carries its own citation; an uncited edge is refused by the corpus tests.

Bioactivities 1

Entries preserve source qualifiers, targets and evidence. Repeated assay names or values are not independent replications; inspect source detail for differences.

AssayResultTarget enzymeSource detail
5-LO Activity Assay from Article 10.1002/cbic.201500446: "Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5-Lipoxygenase Inhibitors."IC50 1.715 uM; ACTIVEUniProtKB:P09917
PMID:26416255
assay
5-LO Activity Assay from Article 10.1002/cbic.201500446: "Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5-Lipoxygenase Inhibitors."
evidence
  • reference
    PMID:26416255
    evidence type
    DATABASE_ASSERTION
    notes
    PubChem BioAssay AID 1801607, deposited by BindingDB; assay type Confirmatory.
call
ACTIVE
measurement type
IC50
value
1.715
units
uM
target enzyme
UniProtKB:P09917

Explore across X-Mech

AntibioticMech (myxochelin A) ↗ MediaIngredientMech (naturalproductmech:mibig-b9324089ad) ↗ TaxonMech: Stigmatella aurantiaca Sg a15 (NCBITaxon:675526) ↗ TaxonMech: Archangium violaceum (NCBITaxon:83451) ↗ TaxonMech: Pseudoalteromonas piscicida (NCBITaxon:43662) ↗ TaxonMech: Myxococcus xanthus DK 1622 (NCBITaxon:246197) ↗ PathwayMech (mibig:BGC0001345) ↗ PathwayMech (mibig:BGC0002324) ↗ PathwayMech (mibig:BGC0002491) ↗

Open questions 1

curator-m920-protein-and-product-scope — Can the m9-20 readout be assigned to this exact stereoisomer, and which clone proteins have experimentally demonstrated myxochelin functions?

Provenance

Source conceptSourceVersion
BGC0001345MIBIG5
BGC0002324MIBIG3
BGC0002491MIBIG3
BGC0002492MIBIG3

This page is generated from data/natural_products/alkaloids/myxochelin-a.yaml, which is generated from the committed inventories. Neither is edited by hand.