title: Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines.
abstract: Nonribosomal peptide synthetases are large enzyme complexes that synthesize a variety of peptide natural products through a thiotemplated mechanism. Assembly of the peptides proceeds through amino acid loading, amide-bond formation and chain translocation, and finally thioester lysis to release the product. The final products are often heavily modified, however, through methylation, epimerization, hydroxylation, heterocyclization, oxidative cross-linking and attachment of sugars. These activities are the province of specialized enzymes (either embedded in the multidomain nonribosomal peptide synthetase structure or standalone).
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. christopher_walsh@hms.harvard.edu
authors.forename: C T
authors.initials: CT
authors.lastname: Walsh
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: T A
authors.initials: TA
authors.lastname: Keating
authors.forename: B K
authors.initials: BK
authors.lastname: Hubbard
authors.forename: H C
authors.initials: HC
authors.lastname: Losey
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: C G
authors.initials: CG
authors.lastname: Marshall
authors.forename: D A
authors.initials: DA
authors.lastname: Miller
authors.forename: H M
authors.initials: HM
authors.lastname: Patel
mesh_terms: D001419:Bacteria / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D016695:Glycosyltransferases; D008780:Methyltransferases / Q000378:metabolism; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism*; D010452:Peptide Biosynthesis; D010441:Peptide Chain Elongation, Translational; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000096:biosynthesis; D011487:Protein Conformation; D019998:Racemases and Epimerases / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D004952:Esters; D009097:Multienzyme Complexes; D010455:Peptides; D010456:Peptides, Cyclic; D003577:Cytochrome P-450 Enzyme System; D008780:Methyltransferases; D016695:Glycosyltransferases; D019998:Racemases and Epimerases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase