Echinomycin

Echinomycin
Names
	Other names Quinomycin A; Levomycin
Identifiers
CAS Number	512-64-1 ;
3D model (JSmol)	Interactive image;
ChemSpider	5257063 ;
ECHA InfoCard	100.164.832
PubChem CID	6857732;
	InChI InChI=1S/C51H64N12O12S2/c1-25(2)38-49(72)74-22-36(59-42(65)34-21-53-30-17-13-15-19-32(30)57-34)44(67)55-28(6)46(69)63(10)40-48(71)62(9)39(26(3)4)50(73)75-23-35(58-41(64)33-20-52-29-16-12-14-18-31(29)56-33)43(66)54-27(5)45(68)60(7)37(47(70)61(38)8)24-77-51(40)76-11/h12-21,25-28,35-40,51H,22-24H2,1-11H3,(H,54,66)(H,55,67)(H,58,64)(H,59,65)/t27-,28-,35+,36+,37-,38-,39-,40+,51?/m0/s1 Key: AUJXLBOHYWTPFV-VITLIGDRSA-N ; InChI=1/C51H64N12O12S2/c1-25(2)38-49(72)74-22-36(59-42(65)34-21-53-30-17-13-15-19-32(30)57-34)44(67)55-28(6)46(69)63(10)40-48(71)62(9)39(26(3)4)50(73)75-23-35(58-41(64)33-20-52-29-16-12-14-18-31(29)56-33)43(66)54-27(5)45(68)60(7)37(47(70)61(38)8)24-77-51(40)76-11/h12-21,25-28,35-40,51H,22-24H2,1-11H3,(H,54,66)(H,55,67)(H,58,64)(H,59,65)/t27-,28-,35+,36+,37-,38-,39-,40+,51?/m0/s1 Key: AUJXLBOHYWTPFV-VITLIGDRBO;
	SMILES C[C@H]1C(=O)N([C@H]2CSC([C@@H](C(=O)N([C@H](C(=O)OC[C@H](C(=O)N1)NC(=O)c3cnc4ccccc4n3)C(C)C)C)N(C(=O)[C@@H](NC(=O)[C@@H](COC(=O)[C@@H](N(C2=O)C)C(C)C)NC(=O)c5cnc6ccccc6n5)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

↑ 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.
↑ 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.
1 2 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.

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[Watanabe-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.

[pmid23856054-2] 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.

[Watanabe2-3] 1 2 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.