Beauveriolide I
(Synonyms: 白僵内酯I) 目录号 : GC46911
A cyclodepsipeptide inhibitor of lipid droplet formation
Cas No.:154491-55-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Beauveriolide I is a cyclodepsipeptide that has been found in Beauveria and an inhibitor of lipid droplet formation.1 It inhibits lipid droplet formation when used at concentrations of 3 and 10 µM, as well as inhibits cholesterol synthesis (IC50 = 0.78 µM), in primary mouse peritoneal macrophages.1,2 Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50 = 6 µM).2
1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)
| Cas No. | 154491-55-1 | SDF | |
| 别名 | 白僵内酯I | ||
| Canonical SMILES | O=C(C[C@@](OC([C@H](NC([C@@H](NC1=O)C)=O)CC(C)C)=O)([H])[C@@H](C)CCCC)N[C@H]1CC2=CC=CC=C2 | ||
| 分子式 | C27H41N3O5 | 分子量 | 487.6 |
| 溶解度 | 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 | 2.0509 mL | 10.2543 mL | 20.5086 mL |
| 5 mM | 0.4102 mL | 2.0509 mL | 4.1017 mL |
| 10 mM | 0.2051 mL | 1.0254 mL | 2.0509 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。
Selective production of fungal Beauveriolide I or III by fermentation in amino acid-supplemented media
J Antibiot (Tokyo) 2002 Dec;55(12):1048-52.PMID:12617514DOI:10.7164/antibiotics.55.1048.
Beauveriolides I and III, cyclic depsipeptides composed of L-Phe, L-Ala, D-Leu and (3S,4S)-3-hydroxy-4-methyloctanoic acid, and L-Phe, L-Ala, L-allo-Ile and (3S,4S)-3-hydroxy-4-methyloctanoic acid, respectively, were previously isolated from the culture broth of fungal Beauveria sp. FO-6979 as inhibitors of macrophage foam cell formation. To improve the production of these compounds by fermentation, the culture conditions were studied. The production of both beauveriolides was increased five to ten folds by fermentation in the culture media containing tryptone. Further study revealed that addition of L-Leu/L-Ile, but not D-Leu/D-allo-Ile, to the culture medium yielded a high and selective production of Beauveriolide I or III. As a result, regardless of their separation difficulty due to the similar physico-chemical properties, a large amount of Beauveriolide I or III was prepared from the culture broth obtained from L-Leu- or L-Ile-supplemented fermentation, respectively, by one step purification using silica gel column chromatography.
Genome mining and biosynthesis of the Acyl-CoA:cholesterol acyltransferase inhibitor Beauveriolide I and III in Cordyceps militaris
J Biotechnol 2020 Feb 10;309:85-91.PMID:31926180DOI:10.1016/j.jbiotec.2020.01.002.
Ascomycete fungi Cordyceps are widely used in traditional Chinese medicine, and numerous investigations have been carried out to uncover their biological activities. However, primary researches on the physiological effects of Cordyceps were committed using crude extracts. At present, there are only a few compounds which were comprehensively characterized from Cordyceps, partial owing to the low production. In order to scientifically take advantage of Cordyceps, we used the strategy of genome mining to discover bioactive compounds from Cordyceps militaris. We found the putative biosynthetic gene cluster of the acyl-CoA:cholesterol acyltransferase inhibitor beauveriolides in the genome of C. militaris, and produced the compounds by heterologous expression in Aspergillus nidulans. Production of Beauveriolide I and III also was detected in both ferment mycelia and fruiting bodies of C. militaris. The possible biosynthetic pathway was proposed. Our studies unveil the active compounds of C. militaris against atherosclerosis and Alzheimer's disease and provide the enzyme resources for the biosynthesis of new cyclodepsipeptide molecules.
The natural products Beauveriolide I and III: a new class of beta-amyloid-lowering compounds
Chembiochem 2009 May 25;10(8):1344-7.PMID:19396893DOI:10.1002/cbic.200900139.
Attacking Alzheimer's by ACAT: The aggregation of beta-amyloid peptides, especially Abeta(42), into senile plaques is a hallmark of Alzheimer's disease (AD). We show that the fungal natural products beauveriolides I and III can potently decrease Abeta secretion from cells expressing human amyloid precursor protein; this offers a potential new scaffold for the development of compounds with proven bioavailability for the treatment of AD.
Discovery and combinatorial synthesis of fungal metabolites beauveriolides, novel antiatherosclerotic agents
Acc Chem Res 2008 Jan;41(1):32-9.PMID:17803269DOI:10.1021/ar700117b.
For discovery of a new type of antiatherosclerotic agents, a cell-based assay of lipid droplet accumulation using primary mouse peritoneal macrophages was conducted as a model of macrophage-derived foam cell accumulation, which occurs in the early stage of atherosclerogenesis. During the screening of microbial metabolites for inhibitors of lipid droplet accumulation, 13-membered cyclodepsipeptides, known Beauveriolide I and new beauveriolide III, were isolated from the culture broth of fungal Beauveria sp. FO-6979, a soil isolate, by solvent extraction, ODS column chromatography, silica gel column chromatography, and preparative HPLC. The structure including the absolute stereochemistry of beauveriolide III was elucidated as cyclo-[(3 S,4 S)-3-hydroxy-4-methyloctanoyl- l-phenylalanyl- l-alanyl- d-alloisoleucyl] by spectral analyses, amino acid analyses, and synthetic methods. Furthermore, the absolute stereochemistry was confirmed by the total synthesis of beauveriolides. Study on the mechanism of action revealed that beauveriolides inhibited macrophage acyl-CoA:cholesterol acyltransferase (ACAT) activity to block the synthesis of cholesteryl ester (CE), leading to a reduction of lipid droplets in macrophages. There are two ACAT isozymes in mammals, ACAT1 and ACAT2. ACAT1 is ubiquitously expressed in most tissues and cells including macrophages, while ACAT2 is expressed predominantly in the liver (hepatocytes) and the intestine (enterocytes). Interestingly, beauveriolides inhibited both ACAT1 and ACAT2 to a similar extent in an enzyme assay that utilized microsomes but inhibited ACAT1 selectively in intact cell-based assays. Beauveriolides proved orally active in both low-density lipoprotein receptor and apolipoprotein E knockout mice, reducing the atheroma lesion of heart and aorta without any side effects such as diarrhea or cytotoxicity to adrenal tissues as observed for many synthetic ACAT inhibitors. To obtain more potent inhibitors, a focused library of beauveriolide analogues was prepared by combinatorial chemistry in which solid-phase assembly of linear depsipeptides was carried out using a 2-chlorotrityl linker, followed by solution-phase cyclization, yielding 104 beauveriolide analogues. Among them, diphenyl derivatives were found to show 10 times more potent inhibition of CE synthesis in macrophages than beauveriolide III. Furthermore, most analogues showed selective ACAT1 inhibition or inhibition of both ACAT1 and ACAT2, but interestingly certain analogues gave selective ACAT2 inhibition. These data indicated that subtle structural differences of the inhibitors could discriminate the active sites of the ACAT1 and ACAT2 isozymes. Efforts of further analogue synthesis would make it possible to obtain highly selective ACAT1/ACAT2 inhibitors.
New rapid screening method for anti-aging compounds using budding yeast and identification of Beauveriolide I as a potent active compound
Biosci Biotechnol Biochem 2012;76(6):1226-8.PMID:22790951DOI:10.1271/bbb.110872.
The chronological lifespan (CLS) of budding yeast is a model for the aging of post-mitotic cells in higher eukaryotes. We report here the development of a new method to assess yeast CLS. The new assay is simple, convenient and labor-saving. We applied this new method to screen natural compounds isolated from mushrooms and discovered Beauveriolide I as a potent anti-aging agent.