851900-99-7Relevant academic research and scientific papers
In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes
Lin, Hening,Fischbach, Michael A.,Liu, David R.,Walsh, Christopher T.
, p. 11075 - 11084 (2005)
The iroA locus encodes five genes (iroB, iroC, iroD, iroE, iroN) that are found in pathogenic Salmonella and Escherichia coli strains. We recently reported that IroB is an enterobactin (Ent) C-glucosyltransferase, converting the siderophore into mono-, di-, and triglucosyl enterobactins (MGE, DGE, and TGE, respectively). Here, we report the characterization of IroD and IroE as esterases for the apo and Fe3+-bound forms of Ent, MGE, DGE, and TGE, and we compare their activities with those of Fes, the previously characterized enterobactin esterase. IroD hydrolyzes both apo and Fe3+-bound siderophores distributively to generate DHB-Ser and/or Glc-DHB-Ser, with higher catalytic efficiencies (kcat/Km) on Fe3+-bound forms, suggesting that IroD is the ferric MGE/DGE esterase responsible for cytoplasmic iron release. Similarly, Fes hydrolyzes ferric Ent more efficiently than apo Ent, confirming Fes is the ferric Ent esterase responsible for Fe 3+ release from ferric Ent. Although each enzyme exhibits lower kcat's processing ferric siderophores, dramatic decreases in K m's for ferric siderophores result in increased catalytic efficiencies. The inability of Fes to efficiently hydrolyze ferric MGE, ferric DGE, or ferric TGE explains the requirement for IroD in the iroA cluster. IroE, in contrast, prefers apo siderophores as substrates and tends to hydrolyze the trilactone just once to produce linearized trimers. These data and the periplasmic location of IroE suggest that it hydrolyzes apo enterobactins while they are being exported. IroD hydrolyzes apo MGE (and DGE) regioselectively to give a single linear trimer product and a single linear dimer product as determined by NMR.
Facile synthesis of salmochelin S1, S2, MGE, DGE, and TGE
Yu, Xiaolong,Dai, Yijing,Yang, Tao,Gagné, Michel R.,Gong, Hegui
supporting information; experimental part, p. 144 - 151 (2011/03/17)
Salmochelin S1, S2, MGE, DGE, and TGE were prepared through amide bond connection of an aryl C-glucosyl acyl chloride (Ar1COCl) and serine ester amines, followed by hydrogenolysis of the per-benzylated precursors. Each synthesis employed a highly diastereoselective Ni-catalyzed Negishi approach to the aryl C-glycoside subunit.
Biosynthetic tailoring of microcin E492m: Post-translational modification affords an antibacterial siderophore-peptide conjugate
Nolan, Elizabeth M.,Fischbach, Michael A.,Koglin, Alexander,Walsh, Christopher T.
, p. 14336 - 14347 (2008/09/17)
The present work reveals that four proteins, MceCDIJ, encoded by the MccE492 gene cluster are responsible for the remarkable post-translational tailoring of microcin E492 (MccE492), an 84-residue protein toxin secreted by Klebsiella pneumonaie RYC492 that targets neighboring Gram-negative species. This modification results in attachment of a linearized and monoglycosylated derivative of enterobactin, a nonribosomal peptide and iron scavenger (siderophore), to the MccE492m C-terminus. MceC and MceD derivatize enterobactin by C-glycosylation at the C5 position of a N-(2,3-dihydroxybenzoyl)serine (DHB-Ser) moiety and regiospecific hydrolysis of an ester linkage in the trilactone scaffold, respectively. Mcel and MceJ form a protein complex that attaches C-glycosylated enterobactins to the C-terminal serine residue of both a C10 model peptide and full-length MccE492. In the enzymatic product, the C-terminal serine residue is covalently attached to the C4′ oxygen of the glucose moiety. Nonenzymatic and base-catalyzed migration of the peptide to the C6′ position affords the C6′ glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures.
