Aurodox
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| Category | Antibiotics |
| Catalog number | BBF-00611 |
| CAS | 12704-90-4 |
| Molecular Weight | 810.97 |
| Molecular Formula | C44H62N2O12 |
| Purity | ≥95% |
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Description
It is produced by the strain of Streptomyces goldiniensis var. goldiniensis. Aurodox is a polyketide antibiotic originally isolated from S. goldiniensis, which inhibits bacterial protein biosynthesis by interrupting the functional cycle of Elongation Factor-Tu (EF-Tu). Aurodox is a type 3 secretion system (T3SS) inhibitor and growth promotor in poultry. 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).
Specification
| Synonyms | Antibiotic X 5108; Goldinodox; Goldinomycin; 1-methyl-Mocimycin; Benzamide; CYT11387 |
| IUPAC Name | (2S)-N-[(2E,4E,6S,7R)-7-[(2S,3S,4R,5R)-3,4-dihydroxy-5-[(1E,3E,5E)-7-(4-hydroxy-1-methyl-2-oxopyridin-3-yl)-6-methyl-7-oxohepta-1,3,5-trienyl]oxolan-2-yl]-6-methoxy-5-methylocta-2,4-dienyl]-2-[(2R,3R,4R,6S)-2,3,4-trihydroxy-5,5-dimethyl-6-[(1E,3Z)-penta-1,3-dienyl]oxan-2-yl]butanamide |
| Canonical SMILES | CCC(C(=O)NCC=CC=C(C)C(C(C)C1C(C(C(O1)C=CC=CC=C(C)C(=O)C2=C(C=CN(C2=O)C)O)O)O)OC)C3(C(C(C(C(O3)C=CC=CC)(C)C)O)O)O |
| InChI | InChI=1S/C44H62N2O12/c1-10-12-14-22-32-43(6,7)39(51)40(52)44(55,58-32)29(11-2)41(53)45-24-18-17-20-27(4)37(56-9)28(5)38-36(50)35(49)31(57-38)21-16-13-15-19-26(3)34(48)33-30(47)23-25-46(8)42(33)54/h10,12-23,25,28-29,31-32,35-40,47,49-52,55H,11,24H2,1-9H3,(H,45,53)/b12-10-,15-13+,18-17+,21-16+,22-14+,26-19+,27-20+/t28-,29-,31-,32+,35+,36+,37-,38+,39+,40-,44-/m1/s1 |
| InChI Key | NTAHMPNXQOYXSX-WKSONYIQSA-N |
Properties
| Appearance | Yellow Amorphous Powder |
| Antibiotic Activity Spectrum | gram-posotive becteria |
| Boiling Point | 930.5°C at 760 mmHg |
| Density | 1.27 g/cm3 |
Reference Reading
1. Conformational change of elongation factor Tu (EF-Tu) induced by antibiotic binding. Crystal structure of the complex between EF-Tu.GDP and aurodox
L Vogeley, J R Mesters, R Hilgenfeld, G J Palm J Biol Chem . 2001 May 18;276(20):17149-55. doi: 10.1074/jbc.M100017200.
Aurodox is a member of the family of kirromycin antibiotics, which inhibit protein biosynthesis by binding to elongation factor Tu (EF-Tu). We have determined the crystal structure of the 1:1:1 complex of Thermus thermophilus EF-Tu with GDP and aurodox to 2.0-A resolution. During its catalytic cycle, EF-Tu adopts two strikingly different conformations depending on the nucleotide bound: the GDP form and the GTP form. In the present structure, a GTP complex-like conformation of EF-Tu is observed, although GDP is bound to the nucleotide-binding site. This is consistent with previous proposals that aurodox fixes EF-Tu on the ribosome by locking it in its GTP form. Binding of EF-Tu.GDP to aminoacyl-tRNA and mutually exclusive binding of kirromycin and elongation factor Ts to EF-Tu can be explained on the basis of the structure. For many previously observed mutations that provide resistance to kirromycin, it can now be understood how they prevent interaction with the antibiotic. An unexpected feature of the structure is the reorientation of the His-85 side chain toward the nucleotide-binding site. We propose that this residue stabilizes the transition state of GTP hydrolysis, explaining the acceleration of the reaction by kirromycin-type antibiotics.
2. Insights into the structure-activity relationship of a type III secretion system inhibitor, aurodox
Hayama Tsutsumi, Akio Abe, Aoi Kimishima, Kamrun Naher, Kazunari Sakai, Asaomi Kuwae, Daichi Hagimoto, Masato Iwatsuki, Yukihiro Asami, Yuki Inahashi, Yoshihiro Watanabe, Masako Honsho Bioorg Med Chem Lett . 2022 Aug 1;69:128779. doi: 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.
3. Characterization of the Mode of Action of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis
Rebecca E McHugh, Andrew J Roe, Paul A Hoskisson, Nicky O'Boyle, James P R Connolly Infect Immun . 2019 Jan 24;87(2):e00595-18. doi: 10.1128/IAI.00595-18.
Recent work has demonstrated that the polyketide natural product Aurodox fromStreptomyces goldiniensisis able to block the pathogenesis of the murine pathogenCitrobacter rodentiumIn 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 enterohemorrhagicEscherichia coliFurthermore, we have used transcriptomic analysis to show that Aurodox inhibits the expression at the transcriptional level by repressing the master regulator,lerOur data support a model in which Aurodox acts upstream oflerand 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.
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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
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
