“Echinomycin”的意思、由来-开放百科全书

词条

Echinomycin

释义

Biosynthesis
References

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| ImageFile=Echinomycin.png
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| IUPACName=
| OtherNames=Quinomycin A; Levomycin
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| 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
| 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
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| StdInChIKey = AUJXLBOHYWTPFV-VITLIGDRSA-N
| RTECS =
|Section2={{Chembox Properties
| Formula=C₅₁H₆₄N₁₂O₁₂S₂
| MolarMass=1101.26 g/mol
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| Density=
| MeltingPt=
| BoilingPt=
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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. ^{{cite journal|last=Watanabe|first=K|author2=Oguri, H |author3=Oikawa, H |title=Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway.|journal=Current Opinion in Chemical Biology|date=April 2009|volume=13|issue=2|pages=189–96|pmid=19278894|doi=10.1016/j.cbpa.2009.02.012}}
2. ^{{cite journal |vauthors=Sato M, Nakazawa T, Tsunematsu Y, Hotta K, Watanabe K |title=Echinomycin biosynthesis |journal=Current Opinion in Chemical Biology |volume=17 |issue=4 |pages=537–45 |year=2013 |pmid=23856054 |doi=10.1016/j.cbpa.2013.06.022 |url=}}
3. ^¹{{cite journal|last=Watanabe|first=K|title=Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.|journal=Nature Chemical Biology|date=August 2006|volume=2|issue=8|pages=423–8|pmid=16799553|doi=10.1038/nchembio803|display-authors=etal}}

2 : Antibiotics|Quinoxalines

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