Enterobactin

Enterobactin (also known as Enterochelin) is a powerful siderophore used to acquire free iron for microbial systems. It is primarily found in gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium. ^[2]

Additional recommended knowledge

How to quickly check pipettes?

Daily Visual Balance Check

What is the Correct Way to Check Repeatability in Balances?

Enterobactin is the strongest siderophore known, binding strongly to the ferric ion (Fe³⁺) with extremely high affinity (K = 10⁵² M^-1). ^[3] 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.

Structure 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] While a number of possible stereoisomers are possible due to the chirality of the serine residues, only the Δ-cis isomer is metabolically active. ^[4]

Mechanism

Iron deficiency in a bacterial cell triggers secretion of enterobactin into the extracellular environment, causing formation of an adduct (FeEnt) as the ferric ion is chelated. 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. ^[5]

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 which compose the molecule. It is known that reduction of the iron occurs (Fe³⁺ to Fe²⁺) in conjunction with this cleavage, but no FeEnt bacterial reductase enzyme has been identified, and the mechanism for this process is still unclear. ^[6]

References

1. ^ Doneanu, Catalin E., Roland K. Strong, and William N. Howald. "Characterization of a Noncovalent Lipocalin Complex by Liquie Chromatography/Electrospray Ionization Mass Spectrometry." Journal of Biomolecular Techniques 15 (2004): 208-212.
2. ^ Dertz, Emily A., Jide Xu, Alain Stintzi, and Kenneth N. Raymond. "Bacillibactin-Mediated Iron Transport in Bacillus Subtilis." Journal of the American Chemical Society 128 (2006): 22-23. .
3. ^ Carrano, Carl J., and Kenneth N. Raymond. "Ferric Ion Sequestering Agents. 2. Kinetics and Mechanism of Iron Removal From Transferrin by Enterobactin and Synthetic Tricatechols." Journal of the American Chemical Society 101 (1979): 5401-5404.
4. ^ Walsh, Christopher T., Jun Liu, Frank Rusnak, and Masahiro Sakaitani. "Molecular Studies on Enzymes in Chorismate Metabolism and the Enterobactin Biosynthetic Pathway." Chemical Reviews 90 (1990): 1105-1129.
5. ^ Raymond, Kenneth N., Emily A. Dertz, and Sanggoo S. Kim. "Bioinorganic Chemistry Special Feature: Enterobactin: an Archetype for Microbial Iron Transport." PNAS 100 (2003): 3584-3588.
6. ^ Ward, Thomas R., Andreas Lutz, Serge P. Parel, Jurgen Eusling, Philipp Gutlich, Peter Buglyo, and Chris Orvig. "An Iron-Based Molecular Redox Switch as a Model for Iron Release From Enterobactin Via the Salicylate Binding Mode." Inorganic Chemistry 38 (1999): 5007-5017.