Validamycin A
(Synonyms: 井冈霉素) 目录号 : GC45135
An inhibitor of trehalase
Cas No.:37248-47-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >60.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Validamycin A is an antifungal agent used to protect rice plants against sheath blight caused by the pathogenic fungus, R. solani, due to its ability to inhibit trehalase, a trehalose-hydrolizing enzyme (Ki = 1.9 nM; IC50 = 0.7 μM). It is also effective against the growth and sporulation of R. cerealis, F. culmorum, and other fungi. This compound has also been used to study trehalase activity and trehalose biosynthesis.
| Cas No. | 37248-47-8 | SDF | |
| 别名 | 井冈霉素 | ||
| Canonical SMILES | O[C@H]([C@H]1O)[C@H](O)[C@@H](CO)O[C@@]1([H])O[C@H]2[C@H](O)[C@@H](O)[C@@H](N[C@@]3([H])C=C(CO)[C@@H](O)[C@H](O)[C@H]3O)C[C@@H]2CO | ||
| 分子式 | C20H35NO13 | 分子量 | 497.5 |
| 溶解度 | DMSO: 2 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | 4°C, protect from light, stored under nitrogen |
| 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 | 2.0101 mL | 10.0503 mL | 20.1005 mL |
| 5 mM | 0.402 mL | 2.0101 mL | 4.0201 mL |
| 10 mM | 0.201 mL | 1.005 mL | 2.0101 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。
Trehalase inhibition by Validamycin A may be a promising target to design new fungicides and insecticides
Pest Manag Sci 2021 Sep;77(9):3832-3835.PMID:33786994DOI:10.1002/ps.6382.
The introduction of insecticides and fungicides in agriculture has improved crop yields and, consequently, the quality of life for many people, especially in what is widely considered as the 'first world'. However, the indiscriminate use of dangerous chemical insecticides has led to pest resistance, human and animal poisoning and environmental pollution. Biochemical and genetic evidence concludes that the non-reducing disaccharide trehalose plays an essential role in the pathobiology of many insects and fungi. Both organisms share identical pathway for trehalose biosynthesis (the TPS/TPP pathway), while a high degree of homology in their trehalose hydrolysis capacity (trehalase activities) has also been demonstrated. In the search for new, effective and environmentally sustainable compounds, a set of trehalase inhibitors has emerged as a potentially interesting antifungal and insecticidal target. In particular, the trehalose analogue, Validamycin A, which has a strong inhibitory effect on several trehalases, has been successfully introduced for the treatment of various diseases caused by insects and fungi. Herein, we review the main features of the specific interaction between Validamycin A and trehalase as well as the expected advantages of the applications based on trehalase inhibition as insecticides and fungicides. © 2021 Society of Chemical Industry.
The Inhibitory Effect of Validamycin A on Aspergillus flavus
Int J Microbiol 2020 Jun 27;2020:3972415.PMID:32676114DOI:10.1155/2020/3972415.
Aspergillus flavus is one of the most common isolates from patients with fungal infections. Aspergillus infection is usually treated with antifungal agents, but side effects of these agents are common. Trehalase is an essential enzyme involved in fungal metabolism, and the trehalase inhibitor, Validamycin A, has been used to prevent fungal infections in agricultural products. In this study, we observed that Validamycin A significantly increased trehalose levels in A. flavus conidia and delayed germination, including decreased fungal adherence. In addition, Validamycin A and amphotericin B showed a combinatorial effect on A. flavus ATCC204304 and clinical isolates with high minimum inhibitory concentrations (MICs) of amphotericin B using checkerboard assays. We observed that Validamycin A and amphotericin B had a synergistic effect on A. flavus strains resistant to amphotericin B. The MICs in the combination of Validamycin A and amphotericin B were at 0.125 μg/mL and 2 μg/mL, respectively. The FICI of Validamycin A and amphotericin B of these clinical isolates was about 0.25-0.28 with synergistic effects. No drug cytotoxicity was observed in human bronchial epithelial cells treated with Validamycin A using LDH-cytotoxicity assays. In conclusion, this study demonstrated that Validamycin A inhibited the growth of A. flavus and delayed conidial germination. Furthermore, the combined effect of Validamycin A with amphotericin B increased A. flavus killing, without significant cytotoxicity to human bronchial epithelial cells. We propose that Validamycin A could potentially be used in vivo as an alternative treatment for A. flavus infections.
Validamycin A Enhances the Interaction Between Neutral Trehalase and 14-3-3 Protein Bmh1 in Fusarium graminearum
Phytopathology 2022 Feb;112(2):290-298.PMID:34156266DOI:10.1094/PHYTO-05-21-0214-R.
In agriculture, Trehalase is considered the main target of the biological fungicide Validamycin A, and the toxicology mechanism of Validamycin A is unknown. 14-3-3 proteins, highly conserved proteins, participate in diverse cellular processes, including enzyme activation, protein localization, and acting as a molecular chaperone. In Saccharomyces cerevisiae, the 14-3-3 protein Bmh1could interact with Nth1 to respond to specific external stimuli. Here, we characterized FgNth, FgBmh1, and FgBmh2 in Fusarium graminearum. ΔFgNth, ΔFgBmh1, and ΔFgBmh2 displayed great growth defects and their peripheral tips hyphae generated more branches when compared with wild-type (WT) PH-1. When exposed to Validamycin A as well as high osmotic and high temperature stresses, ΔFgNth, ΔFgBmh1, and ΔFgBmh2 showed more tolerance than WT. Both ΔFgNth and ΔFgBmh1 displayed reduced deoxynivalenol production but opposite for ΔFgBmh2, and all three deletion mutants showed reduced virulence on wheat coleoptiles. In addition, coimmunoprecipitation (Co-IP) experiments suggested that FgBmh1 and FgBmh2 both interact with FgNth, but no interaction was detected between FgBmh1 and FgBmh2 in our experiments. Further, Validamycin A enhances the interaction between FgBmh1 and FgNth in a positive correlation under concentrations of 1 to 100 μg/ml. In addition, both high osmotic and high temperature stresses promote the interaction between FgBmh1 and FgNth. Co-IP assay also showed that neither FgBmh1 nor FgBmh2 could interact with FgPbs2, a MAPKK kinase in the high-osmolarity glycerol pathway. However, FgBmh2 but not FgBmh1 binds to the heat shock protein FgHsp70 in F. graminearum. Taken together, our results demonstrate that FgNth and FgBmh proteins are involved in growth and responses to external stresses and virulence; and validamycin enhanced the interaction between FgNth and FgBmh1in F. graminearum.
A Validamycin Shunt Pathway for Valienamine Synthesis in Engineered Streptomyces hygroscopicus 5008
ACS Synth Biol 2020 Feb 21;9(2):294-303.PMID:31940432DOI:10.1021/acssynbio.9b00319.
Valienamine is the key functional component of many natural glycosidase inhibitors, including the crop protectant Validamycin A and the clinical antidiabetic agent acarbose. Due to its important biomedical activity, it is also the prominent lead compound for the exploration of therapeutic agents, such as the stronger α-glucosidase inhibitor voglibose. Currently, the main route for obtaining valienamine is a multistep biosynthetic process involving the synthesis and degradation of Validamycin A. Here, we established an alternative, vastly simplified shunt pathway for the direct synthesis of valienamine based on an envisioned non-natural transamination in the Validamycin A producer Streptomyces hygroscopicus 5008. We first identified candidate aminotransferases for the non-natural ketone substrate valienone and conducted molecular evolution in vitro. The WecE enzyme from Escherichia coli was verified to complete the envisioned step with >99.9% enantiomeric excess and was further engineered to produce a 32.6-fold more active mutant, VarB, through protein evolution. Subsequently, two copies of VarB were introduced into the host, and the new shunt pathway produced 0.52 mg/L valienamine after a 96-h fermentation. Our study thus illustrates a dramatically simplified alternative shunt pathway for valienamine production and introduces a promising foundational platform for increasing the production of valienamine and its valuable N-modified derivatives for use in pharmaceutical applications.
Validamycin A Delays Development and Prevents Flight in Aedes aegypti (Diptera: Culicidae)
J Med Entomol 2020 Jul 4;57(4):1096-1103.PMID:31982917DOI:10.1093/jme/tjaa004.
Trehalose is a disaccharide that is the major sugar found in insect hemolymph fluid. Trehalose provides energy, and promotes growth, metamorphosis, stress recovery, chitin synthesis, and insect flight. The hydrolysis of trehalose is under the enzymatic control of the enzyme trehalase. Trehalase is critical to the role of trehalose in insect physiology, and is required for the regulation of metabolism and glucose generation. Trehalase inhibitors represent a novel class of insecticides that have not been fully developed. Here, we tested the ability of trehalose analogues to function as larvacides or adulticides in an important disease vector-Aedes aegypti. We show that Validamycin A, but not 5-thiotrehalose, delays larval and pupal development and prevents flight of adult mosquitoes. Larval mosquitoes treated with Validamycin A were hypoglycemic and pupae had increased levels of trehalose. Treatment also skewed the sex ratio toward male mosquitoes. These data reveal that Validamycin A is a mosquito adulticide that can impair normal development of an important disease vector.