Melithiazol A
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| Category | Antibiotics |
| Catalog number | BBF-01906 |
| CAS | 170894-30-1 |
| Molecular Weight | 422.56 |
| Molecular Formula | C20H26N2O4S2 |
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Description
Melithiazol A is an antibiotic produced by Melittangium lichenicila Mel26, Archangium gephyra Ar 7747 and Myxococcus stipitatus Mx s 64. It is a β-methoxyacrylate (MOA) inhibitor with strong anti-agent activity. Antifungal and cytotoxic agent.
Specification
| Synonyms | Melithiazole A |
| IUPAC Name | methyl (2Z,6E)-3,5-dimethoxy-4-methyl-7-[2-(2-prop-1-en-2-yl-4,5-dihydro-1,3-thiazol-4-yl)-1,3-thiazol-4-yl]hepta-2,6-dienoate |
| Canonical SMILES | CC(C(C=CC1=CSC(=N1)C2CSC(=N2)C(=C)C)OC)C(=CC(=O)OC)OC |
| InChI | InChI=1S/C20H26N2O4S2/c1-12(2)19-22-15(11-28-19)20-21-14(10-27-20)7-8-16(24-4)13(3)17(25-5)9-18(23)26-6/h7-10,13,15-16H,1,11H2,2-6H3/b8-7+,17-9- |
| InChI Key | ANGKCYLBHBLXFP-OIZSJBGPSA-N |
Properties
| Appearance | Oil |
| Antibiotic Activity Spectrum | fungi |
| Boiling Point | 575.4±60.0°C at 760 mmHg |
| Density | 1.2±0.1 g/cm3 |
Reference Reading
1. Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties
F Sasse, B Böhlendorf, M Herrmann, B Kunze, E Forche, H Steinmetz, G Höfle, H Reichenbach J Antibiot (Tokyo). 1999 Aug;52(8):721-9. doi: 10.7164/antibiotics.52.721.
New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.
2. Biochemical characterization of MelJ and MelK
I Müller, R Müller FEBS J. 2006 Aug;273(16):3768-78. doi: 10.1111/j.1742-4658.2006.05385.x.
Melithiazol and myxothiazol are two myxobacterial metabolites that are highly efficient electron transport inhibitors of the respiratory chain. MelJ and MelK encoded in the melithiazol biosynthetic gene cluster were recently shown to be involved in the formation of the methyl ester from a hypothetical amide intermediate. In vivo studies suggest that the structurally highly similar amide myxothiazol A can be used as a substrate mimic of the hypothetical melithiazol amide to characterize the hydrolase MelJ. Both enzymes were produced in Escherichia coli as intein chitin fusion proteins and were purified using affinity chromatography. MelJ was found to catalyse the conversion of the amide myxothiazol to free myxothiazol acid. The formerly unknown myxothiazol acid was purified and used as a substrate for the methyl transferase MelK which methylates the compound using S-adenosyl-methionine as cosubstrate. Sequence analyses suggest that MelJ and MelK are members of the amidase signature family and of a new subclass of methyltransferases, respectively. Kinetic analyses point at a very high substrate specificity for both enzymes. Furthermore, the in vitro reconstitution of a unique mechanism of methyl ester formation found in myxobacteria is reported.
3. A unique mechanism for methyl ester formation via an amide intermediate found in myxobacteria
Inga Müller, Stefan Weinig, Heinrich Steinmetz, Birgitte Kunze, Sheeba Veluthoor, Taifo Mahmud, Rolf Müller Chembiochem. 2006 Aug;7(8):1197-205. doi: 10.1002/cbic.200600057.
Secondary metabolism involves a broad diversity of biochemical reactions that result in a wide variety of biologically active compounds. Terminal amide formation during the biosynthesis of the myxobacterial electron-transport inhibitor, myxothiazol, was analyzed by heterologous expression of the unique nonribosomal-peptide synthetase, MtaG, and incubation with a synthesized substrate mimic. These experiments provide evidence that the terminal amide is formed from a carrier protein-bound myxothiazol acid that is thioesterified to MtaF. This intermediate is transformed to an amide by extension with glycine and subsequent oxidative cleavage by MtaG. The final steps of melithiazol assembly involve a highly similar protein-bound intermediate (attached to MelF, a homologue of MtaF), which is transformed to an amide by MelG (homologue of MtaG). In this study, we also show that the amide moiety of myxothiazol A can be hydrolyzed in vivo to the formerly unknown free myxothiazol acid by heterologous expression of melJ in the myxothiazol producer Stigmatella aurantiaca DW4/3-1. The methyltransferase MelK can finally methylate the acid to give rise to the methyl ester, which is produced as the final product in the melithiazol A biosynthetic pathway. These experiments clarify the role of MelJ and MelK during melithiazol assembly.
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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 ╳
