Aurodox
(Synonyms: 1-methyl-Mocimycin) 目录号 : GC40005A polyketide antibiotic
Cas No.:12704-90-4
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
Aurodox is a polyketide antibiotic originally isolated from S. goldiniensis. [1] It is active against Gram-positive bacteria, including B. megaterium, B. anthracis, and M. hominis (MICs = 0.06, 0.6, and 3-10 µg/ml, respectively), as well as Pneumococcus and Streptomyces species (MICs = 3-12 and 3-30 µg/ml, respectively). It is effective against S. pyogenes infection in mice with a 50% curative dose (CD50) value of 71 mg/kg. Aurodox inhibits bacterial protein synthesis by binding to bacterial elongation factor Tu (EF-Tu) and inhibiting its release from the ribosome. [2][3]
Reference:
[1]. Berger, J., Lehr, H.A., Teitel, S., et al. A new antibiotic X-5108 OF Streptomyces origin. I. Production, isolation and properties. J. Antibiot. (Tokyo) 26(1), 15-22 (1973).
[2]. Wolf, H., Chinali, G., and Parmeggiani, A. Mechanism of the inhibition of protein synthesis by kirromycin. Role of elongation factor Tu and ribosomes. Eur. J. Biochem. 75(1), 67-75 (1977).
[3]. Bhuta, P., and Chládek, S. Stimulation of Escherichia coli elongation factor Tu-dependent GTP hydrolysis by aminoacyl oligonucleotides in the presence of aurodox. FEBS Lett. 122(1), 113-116 (1980).
| Cas No. | 12704-90-4 | SDF | |
| 别名 | 1-methyl-Mocimycin | ||
| 化学名 | (αS,2R,3R,4R,6S)-N-[(2E,4E,6S,7R)-7-[(2S,3S,4R,5R)-5-[(1E,3E,5E)-7-(1,2-dihydro-4-hydroxy-1-methyl-2-oxo-3-pyridinyl)-6-methyl-7-oxo-1,3,5-heptatrien-1-yl]tetrahydro-3,4-dihydroxy-2-furanyl]-6-methoxy-5-methyl-2,4-octadien-1-yl]-α-ethyltetrahydro-2,3,4-trihydroxy-5,5-dimethyl-6-(1E,3Z)-1,3-pentadien-1-yl-2H-pyran-2-acetamide | ||
| 分子式 | C44H62N2O12 | 分子量 | 811 |
| 溶解度 | 1mg/mL in ethanol, also soluble in DMSO or methanol | 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 | 1.233 mL | 6.1652 mL | 12.3305 mL |
| 5 mM | 0.2466 mL | 1.233 mL | 2.4661 mL |
| 10 mM | 0.1233 mL | 0.6165 mL | 1.233 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。
Biosynthesis of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis
Appl Environ Microbiol 2022 Aug 9;88(15):e0069222.PMID:35867559DOI:10.1128/aem.00692-22.
The global increase in antimicrobial-resistant infections means that there is a need to develop new antimicrobial molecules and strategies to combat the issue. Aurodox is a linear polyketide natural product that is produced by Streptomyces goldiniensis, yet little is known about Aurodox biosynthesis or the nature of the biosynthetic gene cluster (BGC) that encodes its production. To gain a deeper understanding of Aurodox biosynthesis by S. goldiniensis, the whole genome of the organism was sequenced, revealing the presence of an 87 kb hybrid polyketide synthase/non-ribosomal peptide synthetase (PKS/NRPS) BGC. The Aurodox BGC shares significant homology with the kirromycin BGC from S. collinus T? 365. However, the genetic organization of the BGC differs significantly. The candidate Aurodox gene cluster was cloned and expressed in a heterologous host to demonstrate that it was responsible for Aurodox biosynthesis and disruption of the primary PKS gene (aurAI) abolished Aurodox production. These data supported a model whereby the initial core biosynthetic reactions involved in Aurodox biosynthesis followed that of kirromycin. Cloning aurM* from S. goldiniensis and expressing this in the kirromycin producer S. collinus T? 365 enabled methylation of the pyridone group, suggesting this is the last step in biosynthesis. This methylation step is also sufficient to confer the unique type III secretion system inhibitory properties to Aurodox. IMPORTANCE Enterohemorrhagic Escherichia coli (EHEC) is a significant global pathogen for which traditional antibiotic treatment is not recommended. Aurodox inhibits the ability of EHEC to establish infection in the host gut through the specific targeting of the type III secretion system while circumventing the induction of toxin production associated with traditional antibiotics. These properties suggest Aurodox could be a promising anti-virulence compound for EHEC, which merits further investigation. Here, we characterized the Aurodox biosynthetic gene cluster from Streptomyces goldiniensis and established the key enzymatic steps of Aurodox biosynthesis that give rise to the unique anti-virulence activity. These data provide the basis for future chemical and genetic approaches to produce Aurodox derivatives with increased efficacy and the potential to engineer novel elfamycins.
Genome sequence of the aurodox-producing bacterium Streptomyces goldiniensis ATCC 21386
Access Microbiol 2022 Aug 19;4(5):acmi000358.PMID:36003359DOI:10.1099/acmi.0.000358.
We report the genome sequence of Streptomyces goldiniensis ATCC 21386, a strain which produces the anti-bacterial and anti-virulence polyketide, Aurodox. The genome of S. goldiniensis ATCC 21386 was sequenced using a multiplatform hybrid approach, revealing a linear genome of ~10 Mbp with a G+C content of 71%. The genome sequence revealed 36 putative biosynthetic gene clusters (BGCs), including a large region of 271 Kbp that was rich in biosynthetic capability. The genome sequence is deposited in DDBJ/EMBL/GenBank with the accession number PRJNA602141.
Insights into the structure-activity relationship of a type III secretion system inhibitor, Aurodox
Bioorg Med Chem Lett 2022 Aug 1;69:128779.PMID:35545199DOI:10.1016/j.bmcl.2022.128779.
Aurodox was originally isolated in 1972 as a linear polyketide compound exhibiting antibacterial activity against Gram-positive bacteria. We have since identified Aurodox as a specific inhibitor of the bacterial type III secretion system (T3SS) using our original screening system for inhibition of T3SS-mediated hemolysis in enteropathogenic Escherichia coli (EPEC). In this research, we synthesized 15 derivatives of Aurodox and evaluated EPEC T3SS inhibitory activity as well as antibacterial activity against EPEC. One of the derivatives was highly selective for T3SS inhibition, equivalent to that of Aurodox, but without exhibiting antibacterial activity (69-fold selectivity). This work revealed the structure-activity relationship for the inhibition of T3SS by Aurodox and suggests that the target of T3SS is distinct from the target for antibacterial activity.
Characterization of the Mode of Action of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis
Infect Immun 2019 Jan 24;87(2):e00595-18.PMID:30455200DOI:10.1128/IAI.00595-18.
Recent work has demonstrated that the polyketide natural product Aurodox from Streptomyces goldiniensis is able to block the pathogenesis of the murine pathogen Citrobacter rodentium In this work, we aimed to gain a better understanding of the mechanism of action of the compound. We show that Aurodox downregulates the expression of the type III secretion systems of enteropathogenic and enterohemorrhagic Escherichia coli Furthermore, we have used transcriptomic analysis to show that Aurodox inhibits the expression at the transcriptional level by repressing the master regulator, ler Our data support a model in which Aurodox acts upstream of ler and not directly on the secretion system itself. Finally, we have shown that Aurodox, unlike some traditional antibiotics, does not induce expression of RecA, which is essential for the production of Shiga toxin. We propose that these properties nominate Aurodox as a promising antivirulence therapy for the treatment of these infections.
Feedback inhibition of the synthesis of an antibiotic: Aurodox (X-5108)
J Antibiot (Tokyo) 1977 Mar;30(3):244-51.PMID:405357DOI:10.7164/antibiotics.30.244.
The effect of Aurodox on its own biosynthesis by Streptomyces goldiniensis was studied. It was found that addition of exogenous Aurodox inhibits further accumulation of Aurodox by the antibiotic-producing culture. Both long term fermentation studies with aurodox-14C and precursor incorporation studies over short time periods indicated that Aurodox synthesis was regulated by feedback inhibition. The concentration of Aurodox required to completely block further synthesis of the antibiotic was about 400 microng/ml. This is the same as the maximum concentration of Aurodox normally accumulated by the culture used in this study. Antibiotic synthesis was inhibited not only by Aurodox but also by some structural analogs of Aurodox including several having no antibacterial activity. This effect was immediate and readily reversible, indicating that it could be due to inhibition of an enzyme(s) involved in the biosynthesis of Aurodox.