Fumitremorgin B
(Synonyms: 烟曲霉毒素B) 目录号 : GC47377
A mycotoxin
Cas No.:12626-17-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fumitremorgin B is a mycotoxin originally isolated from A. fumigatus.1,2 It induces tremors in and is lethal to mice (LD50 = 5.4 mg/kg, i.v.). It is also toxic to brine shrimp (LC50 = 13.6 μg/ml).3 Fumitremorgin B is active against the phytopathogenic fungi B. cinerea, A. solani, A. alternata, C. gloeosporioides, F. solani, F. oxysporum, and G. saubinettii (MICs = 6.25-100 μg/ml). It has antifeedant activity against armyworm (M. separata) larvae when applied to fresh wheat leaves. Fumitremorgin B inhibits the proliferation of U937 and PC3 cells (IC50s = 14.12 and 43.36 μM, respectively).4
1.Yamazaki, M., Suzuki, S., and Miyaki, K.Tremorgenic toxins from Aspergillus fumigatus FresChem. Pharm. Bull. (Tokyo)19(8)1739-1740(1971) 2.Yamazaki, M., and Suzuki, S.Toxicology of tremorgenic mycotoxins, fumitremorgin A and BDev. Toxicol. Environ. Sci.12273-282(1986) 3.Li, X.-J., Zhang, Q., Zhang, A.-L., et al.Metabolites from Aspergillus fumigatus, an endophytic fungus associated with Melia azedarach, and their antifungal, antifeedant, and toxic activitiesJ. Agric. Food Chem.60(13)3424-3431(2012) 4.Wang, Y., Li, Z.-L., Bai, J., et al.2,5-diketopiperazines from the marine-derived fungus Aspergillus fumigatus YK-7Chem. Biodivers.9(2)85-93(2012)
| Cas No. | 12626-17-4 | SDF | |
| 别名 | 烟曲霉毒素B | ||
| Canonical SMILES | COC1=CC=C(C(N2C/C=C(C)\C)=C1)C3=C2[C@H](/C=C(C)\C)N(C([C@@]4([H])N5CCC4)=O)[C@]([C@H]3O)(O)C5=O | ||
| 分子式 | C27H33N3O5 | 分子量 | 479.6 |
| 溶解度 | DMSO: Soluble,Methanol: Soluble | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0851 mL | 10.4254 mL | 20.8507 mL |
| 5 mM | 0.417 mL | 2.0851 mL | 4.1701 mL |
| 10 mM | 0.2085 mL | 1.0425 mL | 2.0851 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Structural basis for endoperoxide-forming oxygenases
Beilstein J Org Chem 2022 Jun 21;18:707-721.PMID:35821691DOI:10.3762/bjoc.18.71.
Endoperoxide natural products are widely distributed in nature and exhibit various biological activities. Due to their chemical features, endoperoxide and endoperoxide-derived secondary metabolites have attracted keen attention in the field of natural products and organic synthesis. In this review, we summarize the structural analyses, mechanistic investigations, and proposed reaction mechanisms of endoperoxide-forming oxygenases, including cyclooxygenase, Fumitremorgin B endoperoxidase (FtmOx1), and the asnovolin A endoperoxygenase NvfI.
On the reaction mechanism of an endoperoxide ring formation by Fumitremorgin B endoperoxidase. The right arrangement makes a difference
Dalton Trans 2019 Nov 21;48(43):16211-16221.PMID:31580360DOI:10.1039/c9dt02581b.
Fumitremorgin B endoperoxidase (FtmF) belongs to 2-oxoglutarate dependent dioxygenases and catalyzes an unusual oxidative reaction of endoperoxide formation at the final stage of biosynthesis of verruculogen - a mycotoxin produced by Aspergillus and Penicillinum strains. The published crystal structure of FtmF (PDB: ), which is of overall good quality, contains a model of the substrate bound in the active site, which, however, has very low occupancy and its conformation does not comply with the small molecule crystal structure. Moreover, a previous computational study that employed a model based on this crystal structure revealed a substantial reaction barrier, which might indicate that the model of FtmF/substrate complex can have serious errors. The purpose of this work was to model with computational methods the structure of the enzyme-substrate complex and to investigate the mechanisms of the enzymatic reaction. Docking, molecular dynamics simulation and DFT results, all indicate the substrate most likely binds in the active site in a configuration very different from that originally suggested. Moreover, for this newly proposed structure of the enzyme-substrate complex, the reaction energy profile is characterised exclusively by low barriers and it successfully explains the observed regiospecificity of the enzymatic process. Finally, a plausible binding site for ascorbate was found and it is suggested that ascorbate is involved in the final step of the FtmF reaction.
Asymmetric abstraction of two chemically-equivalent methylene hydrogens: significant enantioselectivity of endoperoxide presented by Fumitremorgin B endoperoxidase
Phys Chem Chem Phys 2018 Nov 7;20(41):26500-26505.PMID:30306990DOI:10.1039/c8cp05637d.
The combination of the inert C-H bond activation and asymmetric synthesis, especially the transformation of prochiral sp3 precursors to chiral sp3 centers, is a profound challenge. In the present DFT calculations, the unique enantioselectivity in verruculogen biosynthesis catalyzed by Fumitremorgin B endoperoxidase (FtmOx1) has been mechanistically investigated, where a prochiral methylene in Fumitremorgin B is dominantly converted to an R-chiral eight-membered endoperoxy ring. FtmOx1 is the first-reported mononuclear α-ketoglutarate-dependent non-heme iron enzyme responsible for chiral endoperoxide formation, which handles the substrate using a Tyr224 radical resulting from the hydrogen abstraction by an FeIV[double bond, length as m-dash]O species. It is demonstrated that the perfect enantioselectivity of the R-endoperoxy ring originates from the asymmetric abstraction of two chemically-equivalent methylene hydrogens from substrate chain A by the Tyr224 radical and the high conformation stability of the resultant chain A radical due to steric effects. The barrier difference in the abstraction of two hydrogens is 5.6 kcal mol-1. The hydrogen abstraction by the Tyr224 radical is rate-limiting in the FtmOx1 reaction with an overall barrier of 18.6 kcal mol-1. The results obtained here advance the understanding of the chemistry in enantioselectivity, providing a potentially general way for the transformation of prochiral sp3 precursors to chiral sp3 centers.
Insights into the unprecedented epoxidation mechanism of Fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus by QM/MM calculations
Phys Chem Chem Phys 2017 Mar 15;19(11):7668-7677.PMID:28256663DOI:10.1039/c7cp00313g.
Fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus is the first reported α-ketoglutarate-dependent mononuclear non-haem iron enzyme that catalyzes the endoperoxide formation reaction, converting Fumitremorgin B to verruculogen. Experiments reveal that the molecular oxygen (O2) is incorporated into verruculogen without O-O bond scission, which differs from the currently known non-haem iron enzymes, but the mechanistic details are still unclear. In this paper, on the basis of the crystal structures of FtmOx1 in complex with either the co-substrate (α-ketoglutarate) or the substrate (Fumitremorgin B), a ternary complex model of the enzyme-α-ketoglutarate-substrate has been constructed, and combined quantum mechanics and molecular mechanics (QM/MM) calculations have been performed to unravel the novel mechanism of FtmOx1. Our calculations indicate the quintet of the FeIV[double bond, length as m-dash]O complex as the ground state. The FeIV[double bond, length as m-dash]O complex firstly abstracts a hydrogen from the hydroxyl of Tyr228 to initiate the reaction, which corresponds to a lower energy barrier (9.1 kcal mol-1). If the FeIV[double bond, length as m-dash]O complex directly abstracts a hydrogen from C21 of the substrate, the energy barrier would increase to 33.9 kcal mol-1. When Tyr228 was mutated to Ala228, this energy barrier decreases to 24.0 kcal mol-1. In the subsequent reaction, the generated Tyr228 radical abstracts the hydrogen (H2) from C21 of the substrate with an energy barrier of 23.8 kcal mol-1. The second molecular oxygen binds to the C21 radical of the substrate in the active pocket and further completes the epoxidation with an energy barrier of 4.8 kcal mol-1. These results may provide useful information for understanding the reaction mechanism of FtmOx1 and provide guidance for further experimental investigations.
The isolation, purification and identification of Fumitremorgin B produced by Aspergillus fumigatus
Biomed Environ Sci 1996 Mar;9(1):1-11.PMID:8721621doi
Twenty-six strains of Aspergillus fumigatus were screened for toxigenicity for fumitremorgins A and B. Twenty-three of 26 strains can produce Fumitremorgin B in rice medium determined by TLC and HPLC, and no fumitremorgin A was detected. The strains of no. C4104 and no. 3656 were inoculated onto 5 kg of rice media and incubated in a modified procedure. Finally, 4.0 g of Fumitremorgin B was obtained after extraction and purification by modified methods, and was confirmed by TLC, HPLC, spectral analysis together with other physicochemical analysis. This is the first report of the preparation of Fumitremorgin B in China.