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Record Information
Version2.0
Creation Date2010-05-18 14:48:38 UTC
Update Date2014-12-24 20:26:30 UTC
Accession NumberT3D3756
Identification
Common NameEnniatin A
ClassSmall Molecule
DescriptionEnniatins are mycotoxins that appear in nature as a mixture of cyclohexadepsipeptides produced by bacteria, fungi, and plants. They may be found in contaminated cereal crops. Enniatins have various biological activities and can act as enzyme inhibitors, antifungal and antibacterial agents, and immunomodulatory substances. (5, 1)
Compound Type
  • Amide
  • Amine
  • Ester
  • Ether
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(3S,6R,9S,12R,15S,18R)-3,9,15-Tri[(2S)-2-butanyl]-6,12,18-triisopropyl-4,10,16-trimethyl-1,7,13-trioxa-4,10,16-triazacyclooctadecane-2,5,8,11,14,17-hexone
Cyclo((2R)-2-hydroxy-3-methylbutanoyl-N-methyl-L-isoleucyl-(2R)-2-hydroxy-3-methylbutanoyl-N-methyl-L-isoleucyl-(2R)-2-hydroxy-3-methylbutanoyl-N-methyl-L-isoleucyl)
Chemical FormulaC36H63N3O9
Average Molecular Mass681.900 g/mol
Monoisotopic Mass681.456 g/mol
CAS Registry Number2503-13-1
IUPAC Name3-(butan-2-yl)-9,15-dibutyl-4,10,16-trimethyl-6,12,18-tris(propan-2-yl)-1,7,13-trioxa-4,10,16-triazacyclooctadecane-2,5,8,11,14,17-hexone
Traditional Name3,9-dibutyl-6,12,18-triisopropyl-4,10,16-trimethyl-15-(sec-butyl)-1,7,13-trioxa-4,10,16-triazacyclooctadecane-2,5,8,11,14,17-hexone
SMILESCCCCC1N(C)C(=O)C(OC(=O)C(C(C)CC)N(C)C(=O)C(OC(=O)C(CCCC)N(C)C(=O)C(OC1=O)C(C)C)C(C)C)C(C)C
InChI IdentifierInChI=1S/C36H63N3O9/c1-14-17-19-25-34(43)46-28(21(4)5)31(40)37(11)26(20-18-15-2)35(44)47-30(23(8)9)33(42)39(13)27(24(10)16-3)36(45)48-29(22(6)7)32(41)38(25)12/h21-30H,14-20H2,1-13H3
InChI KeyInChIKey=GVDAJJRPXXFXKC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cyclic depsipeptides. These are natural or synthetic compounds having sequences of amino and hydroxy carboxylic acid residues (usually α-amino and α-hydroxy acids) connected in a ring. The residues are commonly but not necessarily regularly alternating.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassPeptidomimetics
Sub ClassDepsipeptides
Direct ParentCyclic depsipeptides
Alternative Parents
Substituents
  • Cyclic depsipeptide
  • Macrolide lactam
  • Alpha-amino acid ester
  • Macrolactam
  • Macrolide
  • Alpha-amino acid or derivatives
  • Tricarboxylic acid or derivatives
  • Tertiary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid ester
  • Lactam
  • Lactone
  • Oxacycle
  • Carboxylic acid derivative
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.011 g/LALOGPS
logP4.79ALOGPS
logP6.46ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)18.8ChemAxon
pKa (Strongest Basic)-5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area139.83 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity180.66 m³·mol⁻¹ChemAxon
Polarizability76.47 ųChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01qi-2026179000-6805902c4adcdc3f7499JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ufr-3391310000-c94f8c1e2007e652b608JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-2392210000-52018945377b92714c65JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0zn9-7090630000-2bcc0b19f9fd488ee14fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01qi-3460901000-5a41b9e52b04791b35cfJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-3931230000-f82d02bb853a65c89f11JSpectraViewer
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (4)
Mechanism of ToxicityEnniatins are toxic due to their ability to act as ionophores, changing ion transport across membranes and disrupting the ionic selectivity of cell walls. In the membrane, enniatins form a dimeric structure and are able to transport monovalent ions (especially K+, Mg2+,Ca2+ and Na+) across the membranes. This effect is particularly harmful in mitochondrial membranes, resulting in the uncoupling of oxidative phosphorylation. They are also know to inhibit several enzymes, including acyl coenzyme A:cholesterol acyltransferase and cyclic nucleotide phosphodiesterase. Enniatins are cytotoxic and can cause DNA fragmentation, induce apoptosis, and disrupt the ERK signalling pathway. They can also inhibit the activity of membrane-located ATP-binding cassette (ABC) transporters, multidrug pumps which affect the bioavailability of xenobiotics and pharmaceuticals. (1, 2, 3)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesEnniatins are mycotoxins that appear in nature as a mixture of cyclohexadepsipeptides produced by bacteria, fungi, and plants. They may be found in contaminated cereal crops. (5, 1)
Minimum Risk LevelNot Available
Health EffectsEnniatins are cytotoxic. They may also act as antifungal and antibacterial agents, and immunomodulatory substances. (1)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID16727691
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEnniatin
References
Synthesis ReferenceNot Available
MSDST3D3756.pdf
General References
  1. Hyun U, Lee DH, Lee C, Shin CG: Apoptosis induced by enniatins H and MK1688 isolated from Fusarium oxysporum FB1501. Toxicon. 2009 Jun;53(7-8):723-8. doi: 10.1016/j.toxicon.2009.02.012. Epub 2009 Feb 25. [19248798 ]
  2. Watjen W, Debbab A, Hohlfeld A, Chovolou Y, Kampkotter A, Edrada RA, Ebel R, Hakiki A, Mosaddak M, Totzke F, Kubbutat MH, Proksch P: Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. Mol Nutr Food Res. 2009 Apr;53(4):431-40. doi: 10.1002/mnfr.200700428. [19065580 ]
  3. Dornetshuber R, Heffeter P, Sulyok M, Schumacher R, Chiba P, Kopp S, Koellensperger G, Micksche M, Lemmens-Gruber R, Berger W: Interactions between ABC-transport proteins and the secondary Fusarium metabolites enniatin and beauvericin. Mol Nutr Food Res. 2009 Jul;53(7):904-20. doi: 10.1002/mnfr.200800384. [19517454 ]
  4. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  5. Wikipedia. Enniatin. Last updated 10 May 2010. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin.
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Dornetshuber R, Heffeter P, Sulyok M, Schumacher R, Chiba P, Kopp S, Koellensperger G, Micksche M, Lemmens-Gruber R, Berger W: Interactions between ABC-transport proteins and the secondary Fusarium metabolites enniatin and beauvericin. Mol Nutr Food Res. 2009 Jul;53(7):904-20. doi: 10.1002/mnfr.200800384. [19517454 ]
2. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Watjen W, Debbab A, Hohlfeld A, Chovolou Y, Kampkotter A, Edrada RA, Ebel R, Hakiki A, Mosaddak M, Totzke F, Kubbutat MH, Proksch P: Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. Mol Nutr Food Res. 2009 Apr;53(4):431-40. doi: 10.1002/mnfr.200700428. [19065580 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Dornetshuber R, Heffeter P, Sulyok M, Schumacher R, Chiba P, Kopp S, Koellensperger G, Micksche M, Lemmens-Gruber R, Berger W: Interactions between ABC-transport proteins and the secondary Fusarium metabolites enniatin and beauvericin. Mol Nutr Food Res. 2009 Jul;53(7):904-20. doi: 10.1002/mnfr.200800384. [19517454 ]
General Function:
Sterol o-acyltransferase activity
Specific Function:
Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase.
Gene Name:
SOAT1
Uniprot ID:
P35610
Molecular Weight:
64733.975 Da
References
  1. Hyun U, Lee DH, Lee C, Shin CG: Apoptosis induced by enniatins H and MK1688 isolated from Fusarium oxysporum FB1501. Toxicon. 2009 Jun;53(7-8):723-8. doi: 10.1016/j.toxicon.2009.02.012. Epub 2009 Feb 25. [19248798 ]
General Function:
Transferase activity, transferring acyl groups
Specific Function:
Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.
Gene Name:
SOAT2
Uniprot ID:
O75908
Molecular Weight:
59895.735 Da
References
  1. Hyun U, Lee DH, Lee C, Shin CG: Apoptosis induced by enniatins H and MK1688 isolated from Fusarium oxysporum FB1501. Toxicon. 2009 Jun;53(7-8):723-8. doi: 10.1016/j.toxicon.2009.02.012. Epub 2009 Feb 25. [19248798 ]