guanipiperazine A

naturalproductmech:mibig-bc5aed5ce5 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REVIEWED records curator sign-off on identity, structure, filing class and producer claims; DEPRECATED retains a superseded or out-of-scope record.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 InChIKey	OZZPJWGWLXYCFI-KBPBESRZSA-N
SMILES	NC1=NC2=C([NH]C(C3=CC4=CC(=C3O)OC3=CC=C(C=C3)C[C@H]3CN[C@H](CN3)C4)=N2)C(=O)[NH]1
Stereochemistry	fully defined
Cross-references	npatlas:NPA033117

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, from MIBiG.

Producer organisms 1

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.

Taxon	Basis	Cluster	Evidence
Streptomyces chrestomyceticus NCBITaxon:68185	SOURCE_ASSERTION	mibig:BGC0002582	PMID:34164059

Occurrences 1

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.

Taxon	Source	Reference
Streptomyces chrestomyceticus NCBITaxon:68185	LOTUS	DOI:10.1039/D0SC06135B

Biosynthetic gene clusters 1

Accession	Host	Locus evidence	Genome
mibig:BGC0002582	Streptomyces chrestomyceticus NCBITaxon:68185	CLUSTER_DEMONSTRATED	genbank:MW051641.1

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.

Step	Enzyme	Substrate → product	Evidence
1	GupB NRPS-like carboxylic acid reductase NCBIProtein:QUF98525.1	CHEBI:17895 → ungrounded	DOI:10.1039/D0SC06135B
2	GupA F420H2-dependent reductase NCBIProtein:QUF98524.1	ungrounded → ungrounded	DOI:10.1039/D0SC06135B
3	GupC cytochrome P450 NCBIProtein:QUF98526.1	ungrounded → ungrounded	DOI:10.1039/D0SC06135B
4	GupD cytochrome P450 guaninyl transferase NCBIProtein:QUF98527.1	CHEBI:15996 → naturalproductmech:mibig-bc5aed5ce5	DOI:10.1039/D0SC06135B

Step 1: GupB activates two L-tyrosine molecules, reduces them to the corresponding amino aldehydes, and is proposed to form imine intermediate 5 after condensation and dehydration. GupB enzyme_id is grounded to the native GenPept accession NCBIProtein:QUF98525.1 (UniParc UPI001BEE5CB3 archives QUF98525.1 with an active EMBL MW051641.1 cross-reference only and no UniProtKB entry).

Step 2: GupA reduces proposed imine intermediate 5 to piperazine intermediate 4. Both numbered intermediates are left out of the structured substrate and product fields because no exact stable chemical CURIEs were selected. GupA enzyme_id is grounded to the native GenPept accession NCBIProtein:QUF98524.1 (UniParc UPI0019D1AFCC archives QUF98524.1 with an active EMBL MW051641.1 cross-reference only and no UniProtKB entry).

Step 3: GupC oxidizes piperazine intermediate 4 to strained piperazine intermediate 6 by intramolecular C-O bond formation. Both numbered intermediates are left out of the structured substrate and product fields because no exact stable chemical CURIEs were selected. GupC enzyme_id is grounded to the native GenPept accession NCBIProtein:QUF98526.1 (UniParc UPI001BEEC1A1 archives QUF98526.1 with an active EMBL MW051641.1 cross-reference only and no UniProtKB entry).

Step 4: GupD uses GTP as the guanine donor and couples it to strained piperazine intermediate 6, yielding guanipiperazine A through a C-C linkage and guanipiperazine B through a C-O linkage. The intermediate is left out of the structured substrate field because no exact stable chemical CURIE was selected. GupD enzyme_id is grounded to the native GenPept accession NCBIProtein:QUF98527.1 (UniParc UPI001BEFDD7C archives QUF98527.1 with an active EMBL MW051641.1 cross-reference only and no UniProtKB entry).

Mechanism & Biosynthesis Overview

Causal graph — biosynthesis 10 nodes, 9 edges

Streptomyces chrestomyceticus GupA-D assemble guanipiperazine A from L-tyrosine through a piperazine core and a final GTP-dependent guaninylation.

Subject	Predicate	Object	Notes	Evidence
L-tyrosine	is activated and reduced by	GupB	GupB is proposed to activate and reduce two L-tyrosines to amino aldehydes that condense and dehydrate into imine intermediate 5.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98525.1 https://www.uniprot.org/uniparc/UPI001BEE5CB3 reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupB activates and reduces two l-tyrosine molecules notes Shi et al. showed L-tyrosine preference in vitro and proposed that the NRPS-like CAR GupB activates and reduces two L-tyrosines to the amino aldehydes that condense into imine intermediate 5. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupB non-ribosomal peptide synthetase CDS at MW051641.1:548..3772 with protein_id QUF98525.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98525.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98525.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 non-ribosomal peptide synthetase sequence assigned here to GupB; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEE5CB3 evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98525.1 notes UniParc UPI001BEE5CB3 archives the exact 1,074 aa Streptomyces chrestomyceticus NA04264 GupB non-ribosomal peptide synthetase sequence (EMBL MW051641.1:548..3772, protein QUF98525.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98525.1.
GupB	forms	proposed imine intermediate 5	Imine intermediate 5 is proposed; without GupA it can be spontaneously overoxidized to the observed shunt product 3.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98525.1 https://www.uniprot.org/uniparc/UPI001BEE5CB3 reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupB activates and reduces two l-tyrosine molecules notes Shi et al. showed L-tyrosine preference in vitro and proposed that the NRPS-like CAR GupB activates and reduces two L-tyrosines to the amino aldehydes that condense into imine intermediate 5. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupB non-ribosomal peptide synthetase CDS at MW051641.1:548..3772 with protein_id QUF98525.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98525.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98525.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 non-ribosomal peptide synthetase sequence assigned here to GupB; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEE5CB3 evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98525.1 notes UniParc UPI001BEE5CB3 archives the exact 1,074 aa Streptomyces chrestomyceticus NA04264 GupB non-ribosomal peptide synthetase sequence (EMBL MW051641.1:548..3772, protein QUF98525.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98525.1.
proposed imine intermediate 5	is reduced by	GupA		DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98524.1 https://www.uniprot.org/uniparc/UPI0019D1AFCC reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupA is required for the formation of 4 notes Shi et al. used heterologous expression and in vitro reconstitution to assign the F420H2-dependent reductase GupA to reduction of the proposed imine intermediate 5 into piperazine intermediate 4. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupA F420H2-dependent reductase CDS at MW051641.1:1..489 with protein_id QUF98524.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98524.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98524.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 F420H2-dependent reductase sequence assigned here to GupA; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI0019D1AFCC evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98524.1 notes UniParc UPI0019D1AFCC archives the exact 162 aa Streptomyces chrestomyceticus NA04264 GupA F420H2-dependent reductase sequence (EMBL MW051641.1:1..489, protein QUF98524.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98524.1.
GupA	forms	piperazine intermediate 4	Co-expression of gupB and gupA produced intermediate 4, and in vitro reconstitution observed production of 4 only after GupA, F420, and F420H2 regeneration were added.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98524.1 https://www.uniprot.org/uniparc/UPI0019D1AFCC reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupA is required for the formation of 4 notes Shi et al. used heterologous expression and in vitro reconstitution to assign the F420H2-dependent reductase GupA to reduction of the proposed imine intermediate 5 into piperazine intermediate 4. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupA F420H2-dependent reductase CDS at MW051641.1:1..489 with protein_id QUF98524.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98524.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98524.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 F420H2-dependent reductase sequence assigned here to GupA; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI0019D1AFCC evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98524.1 notes UniParc UPI0019D1AFCC archives the exact 162 aa Streptomyces chrestomyceticus NA04264 GupA F420H2-dependent reductase sequence (EMBL MW051641.1:1..489, protein QUF98524.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98524.1.
piperazine intermediate 4	is oxidized by	GupC		DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98526.1 https://www.uniprot.org/uniparc/UPI001BEEC1A1 reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupC catalyzes the intramolecular C–O bond formation notes Shi et al. found that the gupC deletion strain accumulated compound 4 and reconstituted GupC in vitro as the P450 that oxidizes compound 4 to strained piperazine intermediate 6. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupC cytochrome P450 CDS at MW051641.1:3769..5022 with protein_id QUF98526.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98526.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98526.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 cytochrome P450 sequence assigned here to GupC; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEEC1A1 evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98526.1 notes UniParc UPI001BEEC1A1 archives the exact 417 aa Streptomyces chrestomyceticus NA04264 GupC cytochrome P450 sequence (EMBL MW051641.1:3769..5022, protein QUF98526.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98526.1.
GupC	forms	strained piperazine intermediate 6	Deleting gupD accumulated compound 6, and the in vitro GupC reaction consumed compound 4 while compound 6 appeared.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98526.1 https://www.uniprot.org/uniparc/UPI001BEEC1A1 reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupC catalyzes the intramolecular C–O bond formation notes Shi et al. found that the gupC deletion strain accumulated compound 4 and reconstituted GupC in vitro as the P450 that oxidizes compound 4 to strained piperazine intermediate 6. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupC cytochrome P450 CDS at MW051641.1:3769..5022 with protein_id QUF98526.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98526.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98526.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 cytochrome P450 sequence assigned here to GupC; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEEC1A1 evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98526.1 notes UniParc UPI001BEEC1A1 archives the exact 417 aa Streptomyces chrestomyceticus NA04264 GupC cytochrome P450 sequence (EMBL MW051641.1:3769..5022, protein QUF98526.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98526.1.
strained piperazine intermediate 6	is guaninylated by	GupD		DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 https://www.uniprot.org/uniparc/UPI001BEFDD7C reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupD acts as a guaninyl transferase notes Shi et al. showed in vivo and in vitro that P450 GupD couples compound 6 with GTP to form guanipiperazines A and B through alternative C-C and C-O linkages. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 CDS at MW051641.1:5103..6332 with protein_id QUF98527.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98527.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 cytochrome P450 sequence assigned here to GupD; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEFDD7C evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98527.1 notes UniParc UPI001BEFDD7C archives the exact 409 aa Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 sequence (EMBL MW051641.1:5103..6332, protein QUF98527.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98527.1.
GTP	is used by	GupD	GupD accepts GTP as substrate for guaninylation of compound 6.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 https://www.uniprot.org/uniparc/UPI001BEFDD7C reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupD acts as a guaninyl transferase notes Shi et al. showed in vivo and in vitro that P450 GupD couples compound 6 with GTP to form guanipiperazines A and B through alternative C-C and C-O linkages. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 CDS at MW051641.1:5103..6332 with protein_id QUF98527.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98527.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 cytochrome P450 sequence assigned here to GupD; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEFDD7C evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98527.1 notes UniParc UPI001BEFDD7C archives the exact 409 aa Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 sequence (EMBL MW051641.1:5103..6332, protein QUF98527.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98527.1.
GupD	forms	guanipiperazine A	GupD couples compound 6 with GTP to form guanipiperazine A and the alternative O-linked product guanipiperazine B.	DOI:10.1039/D0SC06135B https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 https://www.uniprot.org/uniparc/UPI001BEFDD7C reference DOI:10.1039/D0SC06135B evidence type PRIMARY_EXPERIMENT snippet GupD acts as a guaninyl transferase notes Shi et al. showed in vivo and in vitro that P450 GupD couples compound 6 with GTP to form guanipiperazines A and B through alternative C-C and C-O linkages. reference https://mibig.secondarymetabolites.org/repository/BGC0002582.3/BGC0002582.gbk evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes MIBiG BGC0002582.3 places the Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 CDS at MW051641.1:5103..6332 with protein_id QUF98527.1. reference https://www.ncbi.nlm.nih.gov/protein/QUF98527.1 evidence type DATABASE_ASSERTION retrieved on 2026-10-01 notes NCBI GenPept QUF98527.1 is the Streptomyces chrestomyceticus NA04264 MW051641.1 cytochrome P450 sequence assigned here to GupD; no UniProtKB entry resolved for this accession or for MW051641.1. reference https://www.uniprot.org/uniparc/UPI001BEFDD7C evidence type DATABASE_ASSERTION retrieved on 2026-10-23 snippet QUF98527.1 notes UniParc UPI001BEFDD7C archives the exact 409 aa Streptomyces chrestomyceticus NA04264 GupD cytochrome P450 sequence (EMBL MW051641.1:5103..6332, protein QUF98527.1) with an active EMBL cross-reference only and no UniProtKB cross-reference, confirming no UniProtKB accession resolves for QUF98527.1.

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

Explore across X-Mech

AntibioticMech (guanipiperazine A) ↗ MediaIngredientMech (naturalproductmech:mibig-bc5aed5ce5) ↗ TaxonMech: Streptomyces chrestomyceticus (NCBITaxon:68185) ↗ PathwayMech (mibig:BGC0002582) ↗

Provenance

Source concept	Source	Version
BGC0002582	MIBIG	3

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