Epithienamycin A
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| Category | Antibiotics |
| Catalog number | BBF-00844 |
| CAS | 63582-78-5 |
| Molecular Weight | 314.36 |
| Molecular Formula | C13H18N2O5S |
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Description
Epithienamycin A is a carbapenem antibiotic produced by Streptomyces flavogriseus MA-4434 and MB-4638. It has anti-gram-positive bacteria and anti-gram-negative bacteria activity.
Specification
| IUPAC Name | (5R,6R)-3-(2-acetamidoethylsulfanyl)-6-[(1S)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| Canonical SMILES | CC(C1C2CC(=C(N2C1=O)C(=O)O)SCCNC(=O)C)O |
| InChI | InChI=1S/C13H18N2O5S/c1-6(16)10-8-5-9(21-4-3-14-7(2)17)11(13(19)20)15(8)12(10)18/h6,8,10,16H,3-5H2,1-2H3,(H,14,17)(H,19,20)/t6-,8+,10-/m0/s1 |
| InChI Key | VUDXUIMGYZQRKK-IONOHQLYSA-N |
Properties
| Antibiotic Activity Spectrum | Gram-positive bacteria; Gram-negative bacteria |
Reference Reading
1. Comparative analysis of a cryptic thienamycin-like gene cluster identified in Streptomyces flavogriseus by genome mining
Gloria Blanco Arch Microbiol. 2012 Jun;194(6):549-55. doi: 10.1007/s00203-011-0781-y. Epub 2011 Dec 27.
In silico database searches allowed the identification in the S. flavogriseus ATCC 33331 genome of a carbapenem gene cluster highly related to the S. cattleya thienamycin one. This is the second cluster found for a complex highly substituted carbapenem. Comparative analysis revealed that both gene clusters display a high degree of synteny in gene organization and in protein conservation. Although the cluster appears to be silent under our laboratory conditions, the putative metabolic product was predicted from bioinformatics analyses using sequence comparison tools. These data, together with previous reports concerning epithienamycins production by S. flavogriseus strains, suggest that the cluster metabolic product might be a thienamycin-like carbapenem, possibly the epimeric epithienamycin. This finding might help in understanding the biosynthetic pathway to thienamycin and other highly substituted carbapenems. It also provides another example of genome mining in Streptomyces sequenced genomes as a powerful approach for novel antibiotic discovery.
2. A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
Seydina M Diene, Lucile Pinault, Sophie Alexandra Baron, Saïd Azza, Nicholas Armstrong, Linda Hadjadj, Eric Chabrière, Jean-Marc Rolain, Pierre Pontarotti, Didier Raoult Sci Rep. 2021 May 12;11(1):10062. doi: 10.1038/s41598-021-89600-x.
Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin.
3. Structural characterization of cobalamin-dependent radical S-adenosylmethionine methylases
Hayley L Knox, Squire J Booker Methods Enzymol. 2022;669:3-27. doi: 10.1016/bs.mie.2021.12.013. Epub 2022 Jan 28.
Cobalamin-dependent radical S-adenosylmethionine (SAM) methylases catalyze key steps in the biosynthesis of numerous biomolecules, including protein cofactors, antibiotics, herbicides, and other natural products, but have remained a relatively understudied subclass of radical SAM enzymes due to their inherent insolubility upon overproduction in Escherichia coli. These enzymes contain two cofactors: a [4Fe-4S] cluster that is ligated by three cysteine residues, and a cobalamin cofactor typically bound by residues in the N-terminal portion of the enzyme. Recent advances in the expression and purification of these enzymes in their active states and with both cofactors present has allowed for more detailed biochemical studies as well as structure determination by X-ray crystallography. Herein, we use KsTsrM and TokK to highlight methods for the structural characterization of cobalamin-dependent radical SAM (RS) enzymes and describe recent advances in in the overproduction and purification of these enzymes.
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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 ╳
