Aflatrem
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| Category | Mycotoxins |
| Catalog number | BBF-04462 |
| CAS | 70553-75-2 |
| Molecular Weight | 501.66 |
| Molecular Formula | C32H39NO4 |
| Purity | 98.0% |
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Description
Aflatrem is the secondary metabolite of Aspergillus flavus. It is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems at low dose. It potentiates the gamma-aminobutyric acid (GABA)-induced chloride current. It is a tremorgenic mycotoxin with acute neurotoxic effect.
Specification
| Synonyms | 4H-3,15a-Epoxy-1-benzoxepino[6',7':6,7]indeno[1,2-b]indol-4-one, 9-(1,1-dimethyl-2-propenyl)-2,3,5b,6,7,7a,8,13,13b,13c,14,15-dodecahydro-5b-hydroxy-2,2,13b,13c-tetramethyl-, (3R,5bS,7aS,13bS,13cR,15aS)-; 9-(1,1-Dimethyl-2-propenyl)-2,3,5b,6,7,7aα,8,13,13b,13c,14,15-dodecahydro-5bβ-hydroxy-2,2,13bβ,13cα-tetramethyl-4H-3β,15aβ-epoxy-1-benzoxepino[6',7':6,7]indeno[1,2-b]indol-4-one; α,α-dimethylallylpaspalinine |
| Storage | Store at -20°C |
| IUPAC Name | (1S,4R,5S,16S,19S,23R)-19-hydroxy-4,5,24,24-tetramethyl-12-(2-methylbut-3-en-2-yl)-25,26-dioxa-7-azaheptacyclo[21.2.1.01,20.04,19.05,16.06,14.08,13]hexacosa-6(14),8,10,12,20-pentaen-22-one |
| Canonical SMILES | CC1(C2C(=O)C=C3C4(CCC5CC6=C(C5(C4(CCC3(O2)O1)C)C)NC7=CC=CC(=C67)C(C)(C)C=C)O)C |
| InChI | InChI=1S/C32H39NO4/c1-8-27(2,3)20-10-9-11-21-24(20)19-16-18-12-13-31(35)23-17-22(34)26-28(4,5)37-32(23,36-26)15-14-29(31,6)30(18,7)25(19)33-21/h8-11,17-18,26,33,35H,1,12-16H2,2-7H3/t18-,26-,29+,30+,31+,32-/m0/s1 |
| InChI Key | YVDJBQQJIDPRKP-SLUQHKSNSA-N |
| Source | Aflatrem is a tremorgenic mycotoxin that has been found in the fungus Aspergillus flavus. |
Properties
| Appearance | Yellow Needles |
| Boiling Point | 663.6±55.0°C at 760 mmHg |
| Melting Point | 222-224°C |
| Density | 1.3±0.1 g/cm3 |
| Solubility | Soluble in Chloroform, Methanol |
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, aflatrem inhibits presynaptic high-conductance Ca+2 activated maxi-K+ channels in the smooth muscle. |
Reference Reading
1. Rapid reconstitution of biosynthetic machinery for fungal metabolites in Aspergillus oryzae: total biosynthesis of aflatrem
Koichi Tagami, Atsushi Minami, Ryuya Fujii, Chengwei Liu, Mizuki Tanaka, Katsuya Gomi, Tohru Dairi, Hideaki Oikawa Chembiochem. 2014 Sep 22;15(14):2076-80. doi: 10.1002/cbic.201402195. Epub 2014 Aug 1.
Reconstitution of the biosynthetic machinery for fungal secondary metabolites in Aspergillus oryzae provides an opportunity both for stepwise determination of the biosynthetic pathways and the total biosynthesis of fungal natural products. However, to maximize the utility of the reconstitution system, a simple and rapid strategy for the introduction of heterologous genes into A. oryzae is required. In this study, we demonstrated an effective method for introducing multiple genes involved in the biosynthesis of fungal metabolites by using the expression vectors pUARA2 and pUSA2, each of which contains two cloning sites. The successful introduction of all the aflatrem biosynthetic genes (seven genes in total) after two rounds of transformation enabled the total biosynthesis of aflatrem. This rapid reconstitution strategy will facilitate the functional analysis of the biosynthetic machinery of fungal metabolites.
2. Crystal and mol-ecular structure of aflatrem
Bruno N Lenta, Jules Ngatchou, Patrice T Kenfack, Beate Neumann, Hans-Georg Stammler, Norbert Sewald Acta Crystallogr E Crystallogr Commun. 2015 Oct 17;71(Pt 11):o867-8. doi: 10.1107/S2056989015019040. eCollection 2015 Nov 1.
The crystal structure of the title compound, C32H39NO4, confirms the absolute configuration of the seven chiral centres in the mol-ecule. The molecule has a 1,1-dimethylprop-2-enyl substituent on the indole nucleus and this nucleus shares one edge with the five-membered ring which is, in turn, connected to a sequence of three edge-shared fused rings. The skeleton is completed by the 7,7-trimethyl-6,8-dioxabi-cyclo-[3.2.1]oct-3-en-2-one group connected to the terminal cyclohexene ring. The two cyclohexane rings adopt chair and half-chair conformations, while in the dioxabi-cyclo-[3.2.1]oct-3-en-2-one unit, the six-membered ring has a half-chair conformation. The indole system of the mol-ecule exhibits a tilt of 2.02 (1)° between its two rings. In the crystal, O-H⋯O hydrogen bonds connect mol-ecules into chains along [010]. Weak N-H⋯π inter-actions connect these chains, forming sheets parallel to (10-1).
3. Identification of two aflatrem biosynthesis gene loci in Aspergillus flavus and metabolic engineering of Penicillium paxilli to elucidate their function
Matthew J Nicholson, Albert Koulman, Brendon J Monahan, Beth L Pritchard, Gary A Payne, Barry Scott Appl Environ Microbiol. 2009 Dec;75(23):7469-81. doi: 10.1128/AEM.02146-08. Epub 2009 Oct 2.
Aflatrem is a potent tremorgenic toxin produced by the soil fungus Aspergillus flavus, and a member of a structurally diverse group of fungal secondary metabolites known as indole-diterpenes. Gene clusters for indole-diterpene biosynthesis have recently been described in several species of filamentous fungi. A search of Aspergillus complete genome sequence data identified putative aflatrem gene clusters in the genomes of A. flavus and Aspergillus oryzae. In both species the genes for aflatrem biosynthesis cluster at two discrete loci; the first, ATM1, is telomere proximal on chromosome 5 and contains a cluster of three genes, atmG, atmC, and atmM, and the second, ATM2, is telomere distal on chromosome 7 and contains five genes, atmD, atmQ, atmB, atmA, and atmP. Reverse transcriptase PCR in A. flavus demonstrated that aflatrem biosynthesis transcript levels increased with the onset of aflatrem production. Transfer of atmP and atmQ into Penicillium paxilli paxP and paxQ deletion mutants, known to accumulate paxilline intermediates paspaline and 13-desoxypaxilline, respectively, showed that AtmP is a functional homolog of PaxP and that AtmQ utilizes 13-desoxypaxilline as a substrate to synthesize aflatrem pathway-specific intermediates, paspalicine and paspalinine. We propose a scheme for aflatrem biosynthesis in A. flavus based on these reconstitution experiments in P. paxilli and identification of putative intermediates in wild-type cultures of A. flavus.
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: C32H39NO4
Molecular Weight (Monoisotopic Mass): 501.2879 Da
Molecular Weight (Avergae Mass): 501.6564 Da
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C32H39NO4
Molecular Weight (Monoisotopic Mass): 501.2879 Da
Molecular Weight (Avergae Mass): 501.6564 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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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
