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Showing metabocard for Cyclobutane (HMDB0250638)

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IdentificationTaxonomyOntologyPhysical propertiesSpectraBiological propertiesConcentrationsLinksReferencesenzymes (20) Show 20 proteinsXML
enzymes (20) Show 20 proteins
Record Information
Version5.0
StatusDetected but not Quantified
Creation Date2021-09-11 07:44:00 UTC
Update Date2021-10-01 19:59:04 UTC
HMDB IDHMDB0250638
Secondary Accession NumbersNone
Metabolite Identification
Common NameCyclobutane
Descriptioncyclobutane belongs to the class of organic compounds known as cycloalkanes. These are saturated monocyclic hydrocarbons (with or without side chains). Based on a literature review a significant number of articles have been published on cyclobutane. This compound has been identified in human blood as reported by (PMID: 31557052 ). Cyclobutane is not a naturally occurring metabolite and is only found in those individuals exposed to this compound or its derivatives. Technically Cyclobutane is part of the human exposome. The exposome can be defined as the collection of all the exposures of an individual in a lifetime and how those exposures relate to health. An individual's exposure begins before birth and includes insults from environmental and occupational sources.
Structure
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MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for HMDB0250638 (Cyclobutane)


  Mrv1652309112109442D          

  4  4  0  0  0  0            999 V2000
    0.4125    0.9959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9959    0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4125   -0.1709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1709    0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  2  3  1  0  0  0  0
  3  4  1  0  0  0  0
  1  4  1  0  0  0  0
M  END
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3D MOL for HMDB0250638 (Cyclobutane)

HMDB0250638
     RDKit          3D
Cyclobutane
 12 12  0  0  0  0  0  0  0  0999 V2000
    0.0342    1.0523    0.0697 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0490   -0.0292   -0.0429 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0811   -0.9644    0.4253 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9525   -0.0657   -0.4564 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0836    1.9005   -0.5915 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.2003    1.2464    1.1474 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2367   -0.2277   -1.1009 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8764    0.0629    0.6423 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0206   -1.9885    0.1025 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3053   -0.7471    1.4754 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7048   -0.2627   -1.5065 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9882    0.0234   -0.1644 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  1  1  0
  1  5  1  0
  1  6  1  0
  2  7  1  0
  2  8  1  0
  3  9  1  0
  3 10  1  0
  4 11  1  0
  4 12  1  0
M  END
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3D SDF for HMDB0250638 (Cyclobutane)


  Mrv1652309112109442D          

  4  4  0  0  0  0            999 V2000
    0.4125    0.9959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9959    0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4125   -0.1709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1709    0.4125    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  2  3  1  0  0  0  0
  3  4  1  0  0  0  0
  1  4  1  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0250638

> <DATABASE_NAME>
hmdb

> <SMILES>
C1CCC1

> <INCHI_IDENTIFIER>
InChI=1S/C4H8/c1-2-4-3-1/h1-4H2

> <INCHI_KEY>
PMPVIKIVABFJJI-UHFFFAOYSA-N

> <FORMULA>
C4H8

> <MOLECULAR_WEIGHT>
56.108

> <EXACT_MASS>
56.062600258

> <JCHEM_ACCEPTOR_COUNT>
0

> <JCHEM_ATOM_COUNT>
12

> <JCHEM_AVERAGE_POLARIZABILITY>
7.440946091444798

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
0

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
cyclobutane

> <ALOGPS_LOGP>
2.31

> <JCHEM_LOGP>
1.7782746600000001

> <ALOGPS_LOGS>
-1.44

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
1

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_POLAR_SURFACE_AREA>
0.0

> <JCHEM_REFRACTIVITY>
18.404

> <JCHEM_ROTATABLE_BOND_COUNT>
0

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
2.04e+00 g/l

> <JCHEM_TRADITIONAL_IUPAC>
cyclobutane

> <JCHEM_VEBER_RULE>
1

$$$$
Download

3D-SDF for HMDB0250638 (Cyclobutane)

HMDB0250638
     RDKit          3D
Cyclobutane
 12 12  0  0  0  0  0  0  0  0999 V2000
    0.0342    1.0523    0.0697 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0490   -0.0292   -0.0429 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0811   -0.9644    0.4253 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9525   -0.0657   -0.4564 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0836    1.9005   -0.5915 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.2003    1.2464    1.1474 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2367   -0.2277   -1.1009 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8764    0.0629    0.6423 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0206   -1.9885    0.1025 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3053   -0.7471    1.4754 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7048   -0.2627   -1.5065 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9882    0.0234   -0.1644 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  1  1  0
  1  5  1  0
  1  6  1  0
  2  7  1  0
  2  8  1  0
  3  9  1  0
  3 10  1  0
  4 11  1  0
  4 12  1  0
M  END
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PDB for HMDB0250638 (Cyclobutane)

HEADER    PROTEIN                                 11-SEP-21   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   11-SEP-21         0                                  
HETATM    1  C   UNK     0       0.770   1.859   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0       1.859   0.770   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0       0.770  -0.319   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0      -0.319   0.770   0.000  0.00  0.00           C+0
CONECT    1    2    4                                                       
CONECT    2    1    3                                                       
CONECT    3    2    4                                                       
CONECT    4    3    1                                                       
MASTER        0    0    0    0    0    0    0    0    4    0    8    0
END
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3D PDB for HMDB0250638 (Cyclobutane)

COMPND    HMDB0250638
HETATM    1  C1  UNL     1       0.034   1.052   0.070  1.00  0.00           C  
HETATM    2  C2  UNL     1      -1.049  -0.029  -0.043  1.00  0.00           C  
HETATM    3  C3  UNL     1       0.081  -0.964   0.425  1.00  0.00           C  
HETATM    4  C4  UNL     1       0.953  -0.066  -0.456  1.00  0.00           C  
HETATM    5  H1  UNL     1      -0.084   1.900  -0.592  1.00  0.00           H  
HETATM    6  H2  UNL     1       0.200   1.246   1.147  1.00  0.00           H  
HETATM    7  H3  UNL     1      -1.237  -0.228  -1.101  1.00  0.00           H  
HETATM    8  H4  UNL     1      -1.876   0.063   0.642  1.00  0.00           H  
HETATM    9  H5  UNL     1      -0.021  -1.989   0.103  1.00  0.00           H  
HETATM   10  H6  UNL     1       0.305  -0.747   1.475  1.00  0.00           H  
HETATM   11  H7  UNL     1       0.705  -0.263  -1.507  1.00  0.00           H  
HETATM   12  H8  UNL     1       1.988   0.023  -0.164  1.00  0.00           H  
CONECT    1    2    4    5    6
CONECT    2    3    7    8
CONECT    3    4    9   10
CONECT    4   11   12
END
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SMILES for HMDB0250638 (Cyclobutane)

C1CCC1
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INCHI for HMDB0250638 (Cyclobutane)

InChI=1S/C4H8/c1-2-4-3-1/h1-4H2
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View in JSmolView Stereo Labels
SynonymsNot Available
Chemical FormulaC4H8
Average Molecular Weight56.108
Monoisotopic Molecular Weight56.062600258
IUPAC Namecyclobutane
Traditional Namecyclobutane
CAS Registry NumberNot Available
SMILES
C1CCC1
InChI Identifier
InChI=1S/C4H8/c1-2-4-3-1/h1-4H2
InChI KeyPMPVIKIVABFJJI-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as cycloalkanes. These are saturated monocyclic hydrocarbons (with or without side chains).
KingdomOrganic compounds
Super ClassHydrocarbons
ClassSaturated hydrocarbons
Sub ClassCycloalkanes
Direct ParentCycloalkanes
Alternative ParentsNot Available
Substituents
  • Cycloalkane
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
Biological location
ProcessNot Available
RoleNot Available
Physical Properties
StateNot Available
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
logP2.31ALOGPS
logP1.78ChemAxon
logS-1.4ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity18.4 m³·mol⁻¹ChemAxon
Polarizability7.44 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+118.72730932474
DeepCCS[M-H]-116.83230932474
DeepCCS[M-2H]-152.1230932474
DeepCCS[M+Na]+126.50530932474

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
CyclobutaneC1CCC1477.9Standard polar33892256
CyclobutaneC1CCC1474.5Standard non polar33892256
CyclobutaneC1CCC1461.1Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Cyclobutane GC-MS (Non-derivatized) - 70eV, Positivesplash10-0fb9-9000000000-2fe4682a72cc78e47ea92021-09-23Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Cyclobutane GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 10V, Positive-QTOFsplash10-0a4i-9000000000-92bec535d7fb914a9b6a2021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 20V, Positive-QTOFsplash10-0a4i-9000000000-4b695dfd5c53a71b32832021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 40V, Positive-QTOFsplash10-0a4l-9000000000-c002293349d7a9b574772021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 10V, Negative-QTOFsplash10-0pb9-9000000000-0db78c51279f24216a672021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 20V, Negative-QTOFsplash10-0udi-9000000000-77c13d86dc10b5c878772021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Cyclobutane 40V, Negative-QTOFsplash10-0a4i-9000000000-238cf4cede39075f9dac2021-10-12Wishart LabView Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedNot SpecifiedNot SpecifiedNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDC00010469
Chemspider ID8894
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCyclobutane
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID30377
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Barupal DK, Fiehn O: Generating the Blood Exposome Database Using a Comprehensive Text Mining and Database Fusion Approach. Environ Health Perspect. 2019 Sep;127(9):97008. doi: 10.1289/EHP4713. Epub 2019 Sep 26. [PubMed:31557052 ]

Only showing the first 10 proteins. There are 20 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details
1. Centrin-2
General function:
Involved in calcium ion binding
Specific function:
Plays a fundamental role in microtubule-organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CEP110
Gene Name:
CETN2
Uniprot ID:
P41208
Molecular weight:
19738.3
Enzyme Details
2. DNA damage-binding protein 2
General function:
Involved in damaged DNA binding
Specific function:
Required for DNA repair. Binds to DDB1 to form the UV- damaged DNA-binding protein complex (the UV-DDB complex). The UV- DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1- CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4- ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair
Gene Name:
DDB2
Uniprot ID:
Q92466
Molecular weight:
47863.5
Enzyme Details
3. DNA damage-binding protein 1
General function:
Involved in nucleic acid binding
Specific function:
Required for DNA repair. Binds to DDB2 to form the UV- damaged DNA-binding protein complex (the UV-DDB complex). The UV- DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin- protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2
Gene Name:
DDB1
Uniprot ID:
Q16531
Molecular weight:
126966.9
Enzyme Details
4. O-methyltransferase af390-400
General function:
Not Available
Specific function:
O-methyltransferase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF390-400
Uniprot ID:
A0A067Z9B6
Molecular weight:
44501.415
Enzyme Details
5. Dioxygenase af480
General function:
Not Available
Specific function:
Dioxygenase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF480
Uniprot ID:
Q4WAZ3
Molecular weight:
34230.42
Enzyme Details
6. Stereoselective keto-reductase af490
General function:
Not Available
Specific function:
Stereoselective keto-reductase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF490
Uniprot ID:
Q4WAZ4
Molecular weight:
110953.78
Enzyme Details
7. Monooxygenase af470
General function:
Not Available
Specific function:
Monooxygenase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF470
Uniprot ID:
Q4WAZ2
Molecular weight:
31022.46
Enzyme Details
8. Polyketide transferase af380
General function:
Not Available
Specific function:
Polyketide transferase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF380
Uniprot ID:
Q4WAY4
Molecular weight:
32696.995
Enzyme Details
9. Fumagillin beta-trans-bergamotene synthase af520
General function:
Not Available
Specific function:
Beta-trans-bergamotene synthase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF520
Uniprot ID:
M4VQY9
Molecular weight:
31675.98
Enzyme Details
10. Fumagillin dodecapentaenoate synthase
General function:
Not Available
Specific function:
Dodecapentaenoate synthase; part of the gene cluster that mediates the biosynthesis of fumagillin, a meroterpenoid that has numerous biological activities including irreversible inhibition of human type 2 methionine aminopeptidase (METAP2) (PubMed:23488861, PubMed:24568283). The pathway begins with the conversion of farnesyl pyrophosphate (FPP) to beta-trans-bergamotene by the membrane-bound beta-trans-bergamotene synthase af520 (PubMed:23488861). The initial oxidation of beta-trans-bergamotene by the multifunctional cytochrome P450 monooxygenase af510 involves C-H hydroxylation at the bridgehead C5 position to yield 5R-hydroxyl-beta-trans-bergamotene (PubMed:24568283). Subsequently, a four electron oxidation initiated at C-9 coupled to cleavage of the cyclobutane C5-C8 bond of the bicyclo[3.1.1] core yields the epoxyketone intermediate 5-keto-cordycol (PubMed:24568283). An additional epoxidation reaction also catalyzed by af510 then furnishes the characteristic bisepoxide ketone 5-keto-demethoxyfumagillol (PubMed:24568283). 5-keto-demethoxyfumagillol is then subjected to successive C-6 hydroxylation and O-methylation by the dioxygenase af480 and O-methyltransferase af390-400, respectively, to yield 5-keto-fumagillol, which is then stereoselectively reduced by the keto-reductase af490 to 5R-hydroxy-seco-sesquiterpene (PubMed:24568283). The next step is the polyketide transferase af380-catalyzed transfer of a dodecapentaenoyl group synthesized by the polyketide synthase af370 onto 5R-hydroxy-seco-sesquiterpene which leads to the production of prefumagillin (PubMed:24568283). Finally, oxidative cleavage by the monooxygenase af470 converts prefumagillin to fumagillin (PubMed:24568283).
Gene Name:
AF370
Uniprot ID:
Q4WAY3
Molecular weight:
263574.5

Only showing the first 10 proteins. There are 20 proteins in total.

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