Resomycin A
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Category | Antibiotics |
Catalog number | BBF-02178 |
CAS | |
Molecular Weight | 382.36 |
Molecular Formula | C21H18O7 |
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Description
It is produced by the strain of Streptomyces sp. GW71/2497. Resomycin A showed activity of anti-staphylococcus aureus, Escherichia coli and Streptomyces green, with MIC of about 20 μg/mL.
Specification
IUPAC Name | methyl (1S,2R)-2,5,7-trihydroxy-2-methyl-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate |
Canonical SMILES | CC1(CCC2=C(C3=C(C=C2C1C(=O)OC)C(=O)C4=C(C3=O)C(=CC=C4)O)O)O |
InChI | InChI=1S/C21H18O7/c1-21(27)7-6-9-11(16(21)20(26)28-2)8-12-15(18(9)24)19(25)14-10(17(12)23)4-3-5-13(14)22/h3-5,8,16,22,24,27H,6-7H2,1-2H3/t16-,21-/m1/s1 |
InChI Key | JYCCDRRKNCZUQA-IIBYNOLFSA-N |
Properties
Appearance | Orange Solid |
Reference Reading
1. Overproduction of Ristomycin A by activation of a silent gene cluster in Amycolatopsis japonicum MG417-CF17
Marius Spohn, Norbert Kirchner, Andreas Kulik, Angelika Jochim, Felix Wolf, Patrick Muenzer, Oliver Borst, Harald Gross, Wolfgang Wohlleben, Evi Stegmann Antimicrob Agents Chemother. 2014 Oct;58(10):6185-96. doi: 10.1128/AAC.03512-14. Epub 2014 Aug 11.
The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is Amycolatopsis. However, Amycolatopsis japonicum does not produce an antibiotic under standard laboratory conditions. In contrast to most Amycolatopsis strains, A. japonicum is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the bbr gene from Amycolatopsis balhimycina (bbrAba), into A. japonicum. This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of A. japonicum, 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the in silico prediction that the recombinant A. japonicum/pRM4-bbrAba synthesizes ristomycin A.
2. Enhancing Ristomycin A Production by Overexpression of ParB-Like StrR Family Regulators Controlling the Biosynthesis Genes
Kai Liu, Xin-Rui Hu, Li-Xing Zhao, Yemin Wang, Zixin Deng, Meifeng Tao Appl Environ Microbiol. 2021 Sep 10;87(19):e0106621. doi: 10.1128/AEM.01066-21. Epub 2021 Sep 10.
Amycolatopsis sp. strain TNS106 harbors a ristomycin-biosynthetic gene cluster (asr) in its genome and produces ristomycin A. Deletion of the sole cluster-situated StrR family regulatory gene, asrR, abolished ristomycin A production and the transcription of the asr genes orf5 to orf39. The ristomycin A fermentation titer in Amycolatopsis sp. strain TNS106 was dramatically improved by overexpression of asrR and a heterologous StrR family regulatory gene, bbr, from the balhimycin-biosynthetic gene cluster (BGC) utilizing strong promoters and multiple gene copies. Ristomycin A production was improved by approximately 60-fold, resulting in a fermentation titer of 4.01 g/liter in flask culture, in one of the engineered strains. Overexpression of AsrR and Bbr upregulated transcription of tested asr biosynthetic genes, indicating that these asr genes were positively regulated by AsrR and Bbr. However, only the promoter region of the asrR operon and the intergenic region upstream of orf12 were bound by AsrR and Bbr in gel retardation assays, suggesting that AsrR and Bbr directly regulated the asrR operon and probably orf12 to orf14 but no other asr biosynthetic genes. Further assays with synthetic short probes showed that AsrR and Bbr specifically bound not only probes containing the canonical inverted repeats but also a probe with only one 7-bp element of the inverted repeats in its native context. AsrR and Bbr have an N-terminal ParB-like domain and a central winged helix-turn-helix DNA-binding domain. Site-directed mutations indicated that the N-terminal ParB-like domain was involved in activation of ristomycin A biosynthesis and did not affect the DNA-binding activity of AsrR and Bbr. IMPORTANCE This study showed that overexpression of either a native StrR family regulator (AsrR) or a heterologous StrR family regulator (Bbr) dramatically improved ristomycin A production by increasing the transcription of biosynthetic genes directly or indirectly. The conserved ParB-like domain of AsrR and Bbr was demonstrated to be involved in the regulation of asr BGC expression. These findings provide new insights into the mechanism of StrR family regulators in the regulation of glycopeptide antibiotic biosynthesis. Furthermore, the regulator overexpression plasmids constructed in this study could serve as valuable tools for strain improvement and genome mining for new glycopeptide antibiotics. In addition, ristomycin A is a type III glycopeptide antibiotic clinically used as a diagnostic reagent due to its side effects. The overproduction strains engineered in this study are ideal materials for industrial production of ristomycin A.
3. Elucidation of retention mechanism of dipeptides on a ristocetin A-based chiral stationary phase using a combination of chromatographic and molecular simulation techniques
Ina Varfaj, Margarita V Pershina, Mariya V Stepanova, Roccaldo Sardella, Leonid D Asnin, Andrea Carotti J Chromatogr A. 2022 Jul 19;1675:463158. doi: 10.1016/j.chroma.2022.463158. Epub 2022 May 19.
Two chiral stationary phases virtually reproducing the Nautilus-R column were modeled in silico to study the enantiorecognition mechanism of some selected dipeptides, taking into consideration the two different anchoring alternatives to the silica layer involving the two ristocetin A amino groups. A mobile phase composed of water-methanol (40:60, v/v) was included in the system. The analyses of the trajectories supported the experimental L(LL)
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Bio Calculators
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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳