Disorazol A
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| Category | Antibiotics |
| Catalog number | BBF-01166 |
| CAS | 158181-47-6 |
| Molecular Weight | 758.90 |
| Molecular Formula | C43H54N2O10 |
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Description
It is produced by the strain of Sorangium cellulosum So ce 12. It has antifungal effects on Sclerotinite, Ustilago maydis, Mucor, Rhodotorula, Aspergillus, Trichoderma (MIC is 0.08-0.62 μg/mL).
Specification
| IUPAC Name | (2Z,4E,9Z,23Z,25Z)-12,28-bis[(E)-3-hydroxy-2-methylhex-4-en-2-yl]-20-methoxy-7,13,17,29,33-pentaoxa-34,35-diazatetracyclo[29.2.1.115,18.06,8]pentatriaconta-1(34),2,4,9,15,18(35),21,23,25,31-decaene-14,30-dione |
| Canonical SMILES | CC=CC(C(C)(C)C1CC=CC=CC=CC(CC2=NC(=CO2)C(=O)OC(CC=CC3C(O3)C=CC=CC4=NC(=CO4)C(=O)O1)C(C)(C)C(C=CC)O)OC)O |
| InChI | InChI=1S/C43H54N2O10/c1-8-18-34(46)42(3,4)36-23-14-12-10-11-13-20-29(50-7)26-39-45-31(28-52-39)41(49)55-37(43(5,6)35(47)19-9-2)24-17-22-33-32(53-33)21-15-16-25-38-44-30(27-51-38)40(48)54-36/h8-22,25,27-29,32-37,46-47H,23-24,26H2,1-7H3/b11-10-,14-12-,18-8+,19-9+,20-13?,21-15+,22-17-,25-16- |
| InChI Key | FRFRWOXVYJSPCG-KUALNVSNSA-N |
Reference Reading
1. Disorazoles Block Group A Streptococcal Invasion into Epithelial Cells Via Interference with the Host Factor Ezrin
Katharina Rox, Manfred Rohde, Gursharan Singh Chhatwal, Rolf Müller Cell Chem Biol. 2017 Feb 16;24(2):159-170. doi: 10.1016/j.chembiol.2016.12.011. Epub 2017 Jan 12.
Bacterial pathogens use invasion into human cells as a strategy to escape not only the host's immune response, but also anti-bacterial treatment. This often leads to persistence and enables reinitiation of the infection process at a later time point. Here, we show that a family of myxobacterial metabolites, disorazoles, block invasion of group A Streptococcus (GAS) into human epithelial cells. Mechanistically, disorazoles target ezrin, a host protein involved in linking microfilaments to the membrane, and affect invasion most likely by interfering with dynamic phosphorylation of ezrin. Overall, our study suggests ezrin as a new factor in two different GAS invasion pathways, independent of the already known CD44 pathway, and that disorazoles are promising "pathoblocker" compounds aimed at this additional invasion mechanism.
2. The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt microtubule formation
Ruby Carvalho, Ralph Reid, Nina Viswanathan, Hugo Gramajo, Bryan Julien Gene. 2005 Oct 10;359:91-8. doi: 10.1016/j.gene.2005.06.003.
Disorazoles are polyketides produced by the myxobacterium Sorangium cellulosum So ce12. Their mode of action is to inhibit tubulin polymerization and destabilize microtubules. Using transposon mutagenesis, two mutant strains were identified that produced no disorazoles. Sequencing the DNA flanking the insertions revealed a polyketide synthase gene cluster that would encode three polypeptides, DszA, DszB, and DszC, with DszC containing both nonribosomal peptide synthetase and polyketide synthase modules. The disorazole polyketide synthase modules lack an acyltransferase domain. Instead, a separate gene, dszD, encodes an AT protein, thus revealing that the disorazole gene cluster falls into the trans-AT Type I family of PKS enzymes.
3. Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering
Qiang Tu, Jennifer Herrmann, Shengbiao Hu, Ritesh Raju, Xiaoying Bian, Youming Zhang, Rolf Müller Sci Rep. 2016 Feb 15;6:21066. doi: 10.1038/srep21066.
Disorazol, a macrocyclic polykitide produced by the myxobacterium Sorangium cellulosum So ce12 and it is reported to have potential cytotoxic activity towards several cancer cell lines, including multi-drug resistant cells. The disorazol biosynthetic gene cluster (dis) from Sorangium cellulosum (So ce12) was identified by transposon mutagenesis and cloned in a bacterial artificial chromosome (BAC) library. The 58-kb dis core gene cluster was reconstituted from BACs via Red/ET recombineering and expressed in Myxococcus xanthus DK1622. For the first time ever, a myxobacterial trans-AT polyketide synthase has been expressed heterologously in this study. Expression in M. xanthus allowed us to optimize the yield of several biosynthetic products using promoter engineering. The insertion of an artificial synthetic promoter upstream of the disD gene encoding a discrete acyl transferase (AT), together with an oxidoreductase (Or), resulted in 7-fold increase in disorazol production. The successful reconstitution and expression of the genetic sequences encoding for these promising cytotoxic compounds will allow combinatorial biosynthesis to generate novel disorazol derivatives for further bioactivity evaluation.
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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 ╳
