Verruculogen
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| Category | Mycotoxins |
| Catalog number | BBF-04128 |
| CAS | 12771-72-1 |
| Molecular Weight | 511.57 |
| Molecular Formula | C27H33N3O7 |
| Purity | >95% by HPLC |
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Description
Verruculogen is a tremorgenic mycotoxin isolated from penicillium verruculosu. It can inhibit the K+ channel activated by ca2+, and is a cell cycle inhibitor that prevents M phase division.
Specification
| Synonyms | TR 1 toxin |
| Storage | Store at -20°C |
| IUPAC Name | (9R,14S,17S,23R,24S)-23,24-dihydroxy-5-methoxy-12,12-dimethyl-9-(2-methylprop-1-enyl)-10,11-dioxa-8,15,21-triazahexacyclo[12.10.1.02,7.08,25.015,23.017,21]pentacosa-1(25),2(7),3,5-tetraene-16,22-dione |
| Canonical SMILES | CC(=CC1N2C3=C(C=CC(=C3)OC)C4=C2C(CC(OO1)(C)C)N5C(=O)C6CCCN6C(=O)C5(C4O)O)C |
| InChI | InChI=1S/C27H33N3O7/c1-14(2)11-20-29-18-12-15(35-5)8-9-16(18)21-22(29)19(13-26(3,4)37-36-20)30-24(32)17-7-6-10-28(17)25(33)27(30,34)23(21)31/h8-9,11-12,17,19-20,23,31,34H,6-7,10,13H2,1-5H3/t17-,19-,20+,23-,27+/m0/s1 |
| InChI Key | LRXYHMMJJCTUMY-GWXUGYLUSA-N |
| Source | Verruculogen is a tremorgenic mycotoxin that has been found in fungi of the genera Penicillium and Aspergillus. |
Properties
| Appearance | White Solid |
| Boiling Point | 738.4°C at 760 mmHg |
| Melting Point | 233°C |
| Density | 1.49 g/cm3 |
| Solubility | Soluble in ethanol, methanol, DMF, DMSO |
Toxicity
| Carcinogenicity | No indication of carcinogenicity to humans (not listed by IARC). |
| Mechanism Of Toxicity | Tremorgenic mycotoxins exert their toxic effects by interfering with neurotransmitter release, possibly by causing degeneration of nerve terminals. They are thought to inhibit gamma-aminobutyric acid (GABA) receptors, both pre- and postsynaptic, as well as inhibit transmitter breakdown at the GABA-T receptors. This would initially increase neurotransmitter levels, potentiating the GABA-induced chloride current, then lead to decreased levels of neurotransmitter in the synapse. In addition, verruculogen inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. Verruculogen is also genotoxic and causes DNA damage. |
Reference Reading
1. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells
Estelle Escudier, André Coste, Danièle Rivollet, Marcel Delaforge, Françoise Botterel, Khaled Khoufache, Olivier Puel, Nicolas Loiseau, Catherine Cordonnier, Stéphane Bretagne BMC Microbiol . 2007 Jan 23;7:5. doi: 10.1186/1471-2180-7-5.
Background:The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds.Results:We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10(-8) M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts.Conclusion:Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined.
2. Identification of the verruculogen prenyltransferase FtmPT3 by a combination of chemical, bioinformatic and biochemical approaches
Tianjiao Zhu, Han-Li Ruan, Shu-Ming Li, Beate Wollinsky, Kathrin Mundt Chembiochem . 2012 Nov 26;13(17):2583-92. doi: 10.1002/cbic.201200523.
Previous studies showed that verruculogen is the end product of a biosynthetic gene cluster for fumitremorgin-type alkaloids in Aspergillus fumigatus and Neosartorya fischeri. In this study, we isolated fumitremorgin A from N. fischeri. This led to the identification of the responsible gene, ftmPT3, for O-prenylation of an aliphatic hydroxy group in verruculogen. This gene was found at a different location in the genome of N. fischeri than the identified cluster. The coding sequence of ftmPT3 was amplified by fusion PCR and overexpressed in Escherichia coli. The enzyme product of the soluble His(8)-FtmPT3 with verruculogen and dimethylallyl diphosphate (DMAPP) was identified unequivocally as fumitremorgin A by NMR and MS analyses. K(M) values of FtmPT3 were determined for verruculogen and DMAPP at 5.7 and 61.5 μM, respectively. Average turnover number (k(cat)) was calculated from kinetic parameters of verruculogen and DMAPP to be 0.069 s(-1). FtmPT3 also accepted biosynthetic precursors of fumitremorgin A, for example, fumitremorgin B and 12,13-dihydroxyfumitremorgin C, as substrates and catalyses their prenylation.
3. FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase, catalyses the endoperoxide formation of verruculogen in Aspergillus fumigatus
Hanli Ruan, Shu-Ming Li, Shamil Afiyatullov, Alexander Grundmann, Nicola Steffan Org Biomol Chem . 2009 Oct 7;7(19):4082-7. doi: 10.1039/b908392h.
Verruculogen is a tremorgenic mycotoxin and contains an endoperoxide bond. In this study, we describe the cloning, overexpression and purification of a non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase FtmOx1 from Aspergillus fumigatus, which catalyses the conversion of fumitremorgin B to verruculogen by inserting an endoperoxide bond between two prenyl moieties. Incubation with (18)O(2)-enriched atmosphere demonstrated that both oxygen atoms of the endoperoxide bond are derived from one molecule of O(2). FtmOx1 is the first endoperoxide-forming non-heme Fe(ii) and alpha-ketoglutarate-dependent dioxygenase reported so far. A mechanism of FtmOx1-catalysed verruculogen formation is postulated and discussed.
Spectrum
Predicted LC-MS/MS Spectrum - 10V, Positive
Experimental Conditions
Ionization Mode: Positive
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C27H33N3O7
Molecular Weight (Monoisotopic Mass): 511.2319 Da
Molecular Weight (Avergae Mass): 511.5668 Da
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C27H33N3O7
Molecular Weight (Monoisotopic Mass): 511.2319 Da
Molecular Weight (Avergae Mass): 511.5668 Da
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
