Enterobactin

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PubChem=34231
SMILES=C1C(C(=O)OCC(C(=O)OCC(C(=O)O1)NC(=O)C2=C(C(=CC=C2)O)O)NC(=O)C3=C(C(=CC=C3)O)O)NC(=O)C4=C(C(=CC=C4)O)O
Section2=Chembox Properties
Formula=C₃₀H₂₇N₃O₁₅
MolarMass=669.54648 g/mol
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Enterobactin (also known as Enterochelin) is a high affinity siderophore that acquires iron for microbial systems. It is primarily found in gram-negative bacteria, such as "Escherichia coli" and "Salmonella typhimurium". [cite journal | author = Dertz, Emily A., Jide Xu, Alain Stintzi, and Kenneth N. Raymond | title = Bacillibactin-Mediated Iron Transport in Bacillus Subtilis | journal = J. Am. Chem. Soc. | volume = 128 | year = 2006 | pages = 22–23 | doi = 10.1021/ja055898c]

Enterobactin is the strongest siderophore known, binding to the ferric ion (Fe³⁺) with the affinity (K = 10⁵² M^-1). [cite journal | author = Carrano, Carl J., and Kenneth N. Raymond | title = Ferric Ion Sequestering Agents. 2. Kinetics and Mechanism of Iron Removal From Transferrin by Enterobactin and Synthetic Tricatechols | journal = J. Am. Chem. Soc. | volume = 101 | year = 1979 | pages = 5401–5404 | doi = 10.1021/ja00512a047] This value is substantially larger than even some synthetic metal chelators, such as EDTA (K_f,Fe3+ ~ 10²⁵ M^-1). ^[3] Due to its high affinity, enterobactin is capable of chelating even in environments where the concentration of ferric ion is held very low, such as within living organisms. Pathogenic bacteria can steal iron from other living organisms using this mechanism, even though the concentration of iron is kept extremely low due to the toxicity of free iron.

tructure and Biosynthesis

Chorismic acid, an aromatic amino acid precursor, is converted to 2,3-dihydroxybenzoic acid (DHB) by a series of enzymes, EntA, EntB and EntC. An amide linkage of DHB to L-serine is then catalyzed by EntD, EntE, EntF and EntB. Three molecules of the DHB-Ser formed undergo intermolecular cyclization, yielding enterobactin. ^[5] Whereas a number of possible stereoisomers are possible due to the chirality of the serine residues, only the Δ-cis isomer is metabolically active. [cite journal | author = Walsh, Christopher T., Jun Liu, Frank Rusnak, and Masahiro Sakaitani | title = Molecular Studies on Enzymes in Chorismate Metabolism and the Enterobactin Biosynthetic Pathway | journal = Chemical Reviews | volume = 90 | year = 1990 | pages = 1105–1129 | doi = 10.1021/cr00105a003]

Mechanism

Iron deficiency in bacterial cells triggers secretion of enterobactin into the extracellular environment, causing formation of an coordination complex "FeEnt" wherein ferric ion is chelated to the conjugate base of enterbactin. FepA in the bacterial outer membrane then allows entrance of FeEnt to the bacterial periplasm. FepB,C,D and G all participate in transport of the FeEnt through the inner membrane by means of an ATP-binding cassette transporter. [cite journal | author = Raymond, Kenneth N., Emily A. Dertz, and Sanggoo S. Kim | title = Bioinorganic Chemistry Special Feature: Enterobactin: an Archetype for Microbial Iron Transport | journal = Proc. Nat. Acad. Sci. | volume = 100 | year = 2003 | pages = 3584–3588 | doi = 10.1073/pnas.0630018100 | pmid = 12655062]

Due to the extreme iron binding affinity of enterobactin, it is necessary to cleave FeEnt with ferrienterobactin esterase to remove the iron. This degradation yields three 2,3-dihyroxybenzoyl-L-serine units. Reduction of the iron (Fe³⁺ to Fe²⁺) occurs in conjunction with this cleavage, but no FeEnt bacterial reductase enzyme has been identified, and the mechanism for this process is still unclear. [cite journal | author = Ward, Thomas R., Andreas Lutz, Serge P. Parel, Jurgen Eusling, Philipp Gutlich, Peter Buglyo, and Chris Orvig | title = An Iron-Based Molecular Redox Switch as a Model for Iron Release From Enterobactin Via the Salicylate Binding Mode | journal = Inorg. Chem. | volume = 38 | year = 1999 | pages = 5007–5017 | doi = 10.1021/ic990225e]

History

Enterochelin was discovered by the Gibson group, who named the siderophore "enterochelin." These initial studies established the structure and its relationship to 2,3-dihydroxybenzoic acid. [cite journal | author = I. G. O'Brien, G. B. Cox, F. Gibson | title = Biologically active compounds containing 2,3-dihydroxybenzoic acid and serine formed by "Escherichia coli" | journal = Biochim Biophys Acta | year = 1970 | volume = 201 | pages =453–60]

References