BGC0000976

General information about the BGC

MIBiG accession	BGC0000976
Short description	curacin A biosynthetic gene cluster from Moorea producens 3L
Status	Minimal annotation: no A minimal annotation only contains information on the BGC loci and one or more linked chemical product(s) Completeness: complete Whether the loci encodes everything needed for the pathway producing the compound(s)
Remarks	"Thioesterase results in decarboxylation and desulfonation of the compound. "
Biosynthetic class(es)	NRP Polyketide
Loci	NCBI GenBank: HQ696500.1
Compounds	curacin A
Species	Moorea producens 3L [taxonomy]
References	Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula. Chang Z et al., J Nat Prod (2004) PMID:15332855 Antillatoxin and kalkitoxin, ichthyotoxins from the tropical cyanobacterium Lyngbya majuscula, induce distinct temporal patterns of NMDA receptor-mediated neurotoxicity. Berman FW et al., Toxicon (1999) PMID:10482399 Biosynthesis of radiolabeled curacin A and its rapid and apparently irreversible binding to the colchicine site of tubulin. Verdier-Pinard P et al., Arch Biochem Biophys (1999) PMID:10496976 Structure-activity analysis of the interaction of curacin A, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. Verdier-Pinard P et al., Mol Pharmacol (1998) PMID:9443933 Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogues. Blokhin AV et al., Mol Pharmacol (1995) PMID:7565634 Metabolic coupling of dehydration and decarboxylation in the curacin A pathway: functional identification of a mechanistically diverse enzyme pair. Gu L et al., J Am Chem Soc (2006) PMID:16834357 Crystal structure of the ECH2 catalytic domain of CurF from Lyngbya majuscula. Insights into a decarboxylase involved in polyketide chain beta-branching. Geders TW et al., J Biol Chem (2007) PMID:17928301 Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis. Gu L et al., J Am Chem Soc (2009) PMID:19835378 Conformational switch triggered by alpha-ketoglutarate in a halogenase of curacin A biosynthesis. Khare D et al., Proc Natl Acad Sci U S A (2010) PMID:20660778 Tandem acyl carrier proteins in the curacin biosynthetic pathway promote consecutive multienzyme reactions with a synergistic effect. Gu L et al., Angew Chem Int Ed Engl (2011) PMID:21387490 Terminal alkene formation by the thioesterase of curacin A biosynthesis: structure of a decarboxylating thioesterase. Gehret JJ et al., J Biol Chem (2011) PMID:21357626 Characterization of molecular interactions between ACP and halogenase domains in the Curacin A polyketide synthase. Busche A et al., ACS Chem Biol (2012) PMID:22103656 Structural basis of functional group activation by sulfotransferases in complex metabolic pathways. McCarthy JG et al., ACS Chem Biol (2012) PMID:22991895

Chemical products information

curacin A

Copy SMILES

C₂₃H₃₅N₁O₁S₁

Chemical database entries
NPAtlas
PubCHEM
ChEBI
ChEMBL
ChemSpider

List of genes involved in compound(s) production

Identifiers	Position	Product	Functions	Evidence	Extra
AEE88276.1	1 - 1011 (-)	hypothetical protein			copy AA seq copy Nt seq
AEE88277.1	1426 - 8061 (-)	CurM	Scaffold biosynthesis	Activity assay	copy AA seq copy Nt seq
AEE88278.1	8064 - 13934 (-)	CurL	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88279.1	14019 - 20717 (-)	CurK	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88280.1	20776 - 27672 (-)	CurJ	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88281.1	27740 - 32710 (-)	CurI	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88282.1	32710 - 39309 (-)	CurH	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88283.1	39318 - 44069 (-)	CurG	Scaffold biosynthesis	Sequence-based prediction	copy AA seq copy Nt seq
AEE88284.1	44157 - 53744 (-)	CurF	Scaffold biosynthesis	Activity assay	copy AA seq copy Nt seq
AEE88285.1	53732 - 54496 (-)	CurE	Tailoring (Dehydration)	Activity assay	copy AA seq copy Nt seq
AEE88286.1	54753 - 56012 (-)	CurD	Other enzymatic	Activity assay	copy AA seq copy Nt seq
AEE88287.1	56017 - 57243 (-)	CurC	Other enzymatic	Activity assay	copy AA seq copy Nt seq
AEE88288.1	57295 - 57534 (-)	CurB	Activation / processing	Activity assay	copy AA seq copy Nt seq
AEE88289.1	57553 - 64488 (-)	CurA	Scaffold biosynthesis	Activity assay	copy AA seq copy Nt seq
AEE88290.1	65046 - 65189 (-)	hypothetical protein			copy AA seq copy Nt seq

Polyketide-specific information

Subclass	Unknown
Starter unit	Malonyl-CoA
Cyclic?	no

Polyketide-synthases

Genes	Properties	Modules
AEE88277.1 + AEE88288.1 + AEE88281.1 + AEE88279.1 + AEE88277.1 + AEE88285.1 + AEE88284.1 + AEE88283.1 + AEE88287.1 + AEE88282.1 + AEE88280.1 + AEE88278.1 + AEE88289.1	Synthase subclass: Modular type I Thioesterases: AEE88277.1 (Unknown)	Module ? Genes: AEE88288.1 Core domains: Thiolation (ACP/PCP)
		Module ? Genes: AEE88287.1 Core domains: Ketosynthase Scaffold-modifying domains: Beta-branching
		Module ? Genes: AEE88285.1 Core domains: Enoylreductase
		Module 0 Specificity: Malonyl-CoA Evidence for specificity: Activity assay Genes: AEE88289.1 Core domains: Acyltransferase, Thiolation (ACP/PCP)
		Module 1 Specificity: Malonyl-CoA Evidence for specificity: Activity assay Genes: AEE88289.1 Core domains: Ketosynthase, Acyltransferase, Thiolation (ACP/PCP), Thiolation (ACP/PCP), Thiolation (ACP/PCP)
		Module 2 Genes: AEE88284.1 Core domains: Enoylreductase
		Module 3 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88284.1 Core domains: Ketosynthase, Acyltransferase, Dehydratase, Thiolation (ACP/PCP)
		Module 5 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88283.1 Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Dehydratase, Thiolation (ACP/PCP) KR-domain stereochemistry: D-OH
		Module 6 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88282.1 Core domains: Ketosynthase, Acyltransferase, Dehydratase, Enoylreductase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 7 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88281.1 Core domains: Ketosynthase, Acyltransferase, Dehydratase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 8 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88280.1 Core domains: Ketosynthase, Acyltransferase, Dehydratase, Ketoreductase, Thiolation (ACP/PCP) Scaffold-modifying domains: Methylation KR-domain stereochemistry: L-OH
		Module 9 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88279.1 Core domains: Ketosynthase, Acyltransferase, Dehydratase, Enoylreductase, Ketoreductase, Thiolation (ACP/PCP) KR-domain stereochemistry: L-OH
		Module 10 Specificity: Malonyl-CoA Evidence for specificity: Structure-based inference Genes: AEE88278.1 Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP) Scaffold-modifying domains: Methylation KR-domain stereochemistry: L-OH
		Module 11 Specificity: Malonyl-CoA Evidence for specificity: Activity assay Genes: AEE88277.1 Core domains: Ketosynthase, Acyltransferase, Ketoreductase, Thiolation (ACP/PCP), Thioesterase KR-domain stereochemistry: L-OH

NRP-specific information

Subclass	N/A
Cyclic?	no

NRP-synthases

Gene	Modules
AEE88284.1	Module 4 Specificity: cysteine Evidence for specificity: Structure-based inference Condensation domain type: Unknown

Annotation changelog

MIBiG version	Submitter	Notes
1.0	Hidden contributor (ID: SGC7EMZRHSTY2JHRE5IDTTEF, no GDPR consent given).	Submitted
2.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Migrated from v1.4 Updated compound(s) information (NPAtlas curation)
3.0	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Corrected NRP module activity Removed gene names of 'No gene ID' Removed ketoreductase stereochemistry annotation from modules without ketoreductases Sorted modules by module number Changed amino acid substrates to lower case
3.1	Hidden contributor (ID: AAAAAAAAAAAAAAAAAAAAAAAA, no GDPR consent given).	Update chemical activity to schema version 2.11

Detailed domain annotation

Selected features only

Show module domains

Similar known gene clusters

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