Characterization of SyrC, an aminoacyltransferase shuttling threonyl and chlorothreonyl residues in the syringomycin biosynthetic assembly line.
Syringomycin, a lipopeptidolactone assembled from nine amino acid monomers by four enzymes, SyrB1, SyrB2, SyrC, and SyrE, is a cyclic nonribosomal peptide made by plant-associated Pseudomonas spp. This assembly is unusual because the terminal residue, 4-chlorothreonine, has been proposed to be added in trans since the ninth module of the megasynthetase SyrE lacks an adenylation domain required for Thr/Cl-Thr activation. SyrC is now identified as a Thr/Cl-Thr aminoacyltransferase, shuttling the Thr/Cl-Thr moiety between the pantetheinyl arms of the thiolation domain of SyrB1 and the thiolation domain in module nine of SyrE. SyrC uses Cys224 as a catalytic nucleophile to generate a Thr/Cl-Thr-S-enzyme intermediate during transfer. SyrC joins a growing family of such aminoacyl-shuttling enzymes that also use covalent catalysis to move aminoacyl groups from carrier proteins during coumermycin and coronamic acid biosynthesis.
Singh
Gitanjali M
GM
Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Vaillancourt
Frédéric H
FH
Yin
Jun
J
Walsh
Christopher T
CT
D019881:Aminoacyltransferases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D001692:Biological Transport; D010453:Peptide Synthases / Q000378:metabolism*; D044224:Pseudomonas syringae / Q000201:enzymology; D013912:Threonine / Q000031:analogs & derivatives / Q000378:metabolism*
D001426:Bacterial Proteins; C032677:syringomycin; C090484:4-chlorothreonine; D013912:Threonine; D019881:Aminoacyltransferases; D010453:Peptide Synthases; C094582:SyrC protein, Pseudomonas syringae