Echinomycin

Echinomycin

Names
Other names Quinomycin A; Levomycin
Identifiers
CAS Number	512-64-1
Jmol interactive 3D	Image
PubChem	3197
SMILES CC1C(=O)N(C2CSC(C(C(=O)N(C(C(=O)OCC(C(=O)N1)NC(=O)C3=NC4=CC=CC=C4N=C3)C(C)C)C)N(C(=O)C(NC(=O)C(COC(=O)C(N(C2=O)C)C(C)C)NC(=O)C5=NC6=CC=CC=C6N=C5)C)C)SC)C
Properties
Chemical formula	C51H64N12O12S2
Molar mass	1101.26 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Echinomycin is a peptide antibiotic. It intercalates into DNA at two specific sites, thereby blocking the binding of hypoxia inducible factor 1 alpha (HIF1alpha).

Biosynthesis

Echinomycin is a bis-intercalator peptide and is biosynthesized by a unique nonribosomal peptide synthetase (NRPS).^[1][2] Echinomycin is isolated from various bacteria such as Streptomyces lasalienis. It belongs to a family of quinoxaline antibiotics. There is great interest in this group of compounds because they have very potent antibacterial, anticancer, and antiviral activities.^[3]

The biosynthesis of echinomycin starts with molecule QC. L-tryptophan is the precursor for QC and its biosynthesis parallels the first stage of nikkomycin biosynthesis. After QC is biosynthesized, the adenylation domain-containing Ecm1 activates and transfers QC to FabC using the fatty acid biosynthesis acyl carrier protein (ACP). The first module, Ecm6 accepts the QC-SFabC as the starter unit. Emc7 contains a terminal thioesterase domain which allows the peptide to dimerize and then release. This cyclized product then goes on to Ecm17, an oxioreductase, creating a disulfide bond. The last step in this biosynthesis transforms the disulfide bond into a thioacetal bridge. This transformation takes place with Ecm18, which is quite similar to S-adenosyl-L-methionine (SAM)-dependent methyltransferase.^[3]

References

1. Watanabe, K; Oguri, H; Oikawa, H (April 2009). "Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway.". Current Opinion in Chemical Biology 13 (2): 189–96. doi:10.1016/j.cbpa.2009.02.012. PMID 19278894.
2. Sato M, Nakazawa T, Tsunematsu Y, Hotta K, Watanabe K (2013). "Echinomycin biosynthesis". Current Opinion in Chemical Biology 17 (4): 537–45. doi:10.1016/j.cbpa.2013.06.022. PMID 23856054.
3. Watanabe, K; et al. (August 2006). "Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.". Nature Chemical Biology 2 (8): 423–8. doi:10.1038/nchembio803. PMID 16799553.