Elloramycin
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| Category | Antibiotics |
| Catalog number | BBF-01204 |
| CAS | 97218-42-3 |
| Molecular Weight | 660.62 |
| Molecular Formula | C32H36O15 |
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Description
It is produced by the strain of Streptomyces olivaceus Tu 2353. It has weak activity against gram-positive bacteria, streptomycete and L-1210 leukemic cells, but has no effect on mouse leukemic P388 cells in vivo, and also has a strong inhibition of Streptomyces (including the production of bacteria themselves) activity.
Specification
| Synonyms | Elloramycin A; methyl (6aR,7S,10aR)-3-[(6-deoxy-2,3,4-tri-O-methyl-alpha-L-mannopyranosyl)oxy]-6a,7,12-trihydroxy-8,10a-dimethoxy-1-methyl-6,10,11-trioxo-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate; (6aR)-3-[(2-O,3-O,4-O-Trimethyl-6-deoxy-α-L-mannopyranosyl)oxy]-6,6a,7,10,10a,11-hexahydro-6aα,7α,12-trihydroxy-8,10aα-dimethoxy-1-methyl-6,10,11-trioxo-2-naphthacenecarboxylic acid methyl ester |
| IUPAC Name | methyl (6aR,7S,10aR)-6a,7,12-trihydroxy-8,10a-dimethoxy-1-methyl-6,10,11-trioxo-3-[(2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyloxan-2-yl]oxy-7H-tetracene-2-carboxylate |
| Canonical SMILES | CC1C(C(C(C(O1)OC2=CC3=CC4=C(C(=C3C(=C2C(=O)OC)C)O)C(=O)C5(C(=O)C=C(C(C5(C4=O)O)O)OC)OC)OC)OC)OC |
| InChI | InChI=1S/C32H36O15/c1-12-19-14(10-16(20(12)29(38)44-7)47-30-25(43-6)24(42-5)23(41-4)13(2)46-30)9-15-21(22(19)34)28(37)32(45-8)18(33)11-17(40-3)27(36)31(32,39)26(15)35/h9-11,13,23-25,27,30,34,36,39H,1-8H3/t13-,23-,24+,25+,27+,30-,31+,32+/m0/s1 |
| InChI Key | OYEXGNNKRQPUBW-FJYHMNRNSA-N |
Properties
| Appearance | Dark Yellow Amorphous Powder |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Neoplastics (Tumor) |
| Melting Point | 156 °C |
| Solubility | Soluble in Methanol, Chloroform |
Reference Reading
1. A BioBricks toolbox for metabolic engineering of the tetracenomycin pathway
Jennifer T Nguyen, Kennedy K Riebschleger, Katelyn V Brown, Nina M Gorgijevska, S Eric Nybo Biotechnol J. 2022 Mar;17(3):e2100371. doi: 10.1002/biot.202100371. Epub 2021 Nov 12.
Background/goal/aim: The tetracenomycins are aromatic anticancer polyketides that inhibit peptide translation via binding to the large ribosomal subunit. Here, we expressed the elloramycin biosynthetic gene cluster in the heterologous host Streptomyces coelicolor M1146 to facilitate the downstream production of tetracenomycin analogs. Main methods and major results: We developed a BioBricks genetic toolbox of genetic parts for substrate precursor engineering in S. coelicolor M1146::cos16F4iE. We cloned a series of integrating vectors based on the VWB, TG1, and SV1 integrase systems to interrogate gene expression in the chromosome. We genetically engineered three separate genetic constructs to modulate tetracenomycin biosynthesis: (1) the vhb hemoglobin from obligate aerobe Vitreoscilla stercoraria to improve oxygen utilization; (2) the accA2BE acetyl-CoA carboxylase to enhance condensation of malonyl-CoA; (3) lastly, the sco6196 acyltransferase, which is a "metabolic regulatory switch" responsible for mobilizing triacylglycerols to β-oxidation machinery for acetyl-CoA. In addition, we engineered the tcmO 8-O-methyltransferase and newly identified tcmD 12-O-methyltransferase from Amycolatopsis sp. A23 to generate tetracenomycins C and X. We also co-expressed the tcmO methyltransferase with oxygenase urdE to generate the analog 6-hydroxy-tetracenomycin C. Conclusions and implications: Altogether, this system is compatible with the BioBricks [RFC 10] cloning standard for the co-expression of multiple gene sets for metabolic engineering of Streptomyces coelicolor M1146::cos16F4iE. This production platform improves access to potent analogs, such as tetracenomycin X, and sets the stage for the production of new tetracenomycins via combinatorial biosynthesis.
2. Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis
Angelina Ramos, Carlos Olano, Alfredo F Braña, Carmen Méndez, José A Salas J Bacteriol. 2009 Apr;191(8):2871-5. doi: 10.1128/JB.01747-08. Epub 2009 Feb 20.
The glycosyltransferase ElmGT from Streptomyces olivaceus is involved in the biosynthesis of the antitumor drug elloramycin, and it has been shown to possess a broad deoxysugar recognition pattern, being able to transfer different l- and d-deoxysugars to 8-demethyl-tetracenomycin C, the elloramycin aglycone. Site-directed mutagenesis in residues L309 and N312, located in the alpha/beta/alpha motif within the nucleoside diphosphate-sugar binding region, can be used to modulate the substrate flexibility of ElmGT, making it more precise for transfer of specific deoxysugars.
3. Biosynthesis of elloramycin in Streptomyces olivaceus requires glycosylation by enzymes encoded outside the aglycon cluster
Angelina Ramos, Felipe Lombó, Alfredo F Braña, Jürgen Rohr, Carmen Méndez, José A Salas Microbiology (Reading). 2008 Mar;154(Pt 3):781-788. doi: 10.1099/mic.0.2007/014035-0.
Elloramycin is an anthracycline-like antitumour drug produced by Streptomyces olivaceus Tü2353. Cosmid cos16F4 has been previously shown to direct the biosynthesis of the elloramycin aglycon 8-demethyltetracenomycin C (8-DMTC), but not elloramycin. Sequencing of the 24.2 kb insert in cos16F4 shows the presence of 17 genes involved in elloramycin biosynthesis (elm genes) together with another additional eight ORFs probably not involved in elloramycin biosynthesis. The 17 genes would code for the biosynthesis of the polyketide moiety, sugar transfer, methylation of the tetracyclic ring and the sugar moiety, and export. Four genes (rhaA, rhaB, rhaC and rhaD) encoding the enzymic activities required for the biosynthesis of the sugar l-rhamnose were also identified in the S. olivaceus chromosome. The involvement of this rhamnose gene cluster in elloramycin biosynthesis was demonstrated by insertional inactivation of the rhaB gene, generating a non-producer mutant that accumulates the 8-DMTC C aglycon. Coexpression of cos16F4 with pEM4RO (expressing the four rhamnose biosynthesis genes) in Streptomyces lividans led to the formation of elloramycin, demonstrating that both subclusters are required for elloramycin biosynthesis. These results demonstrate that, in contrast to most of the biosynthesis gene clusters from actinomycetes, genes involved in the biosynthesis of elloramycin are located in two chromosomal loci.
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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 ╳
