Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines.
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).
Walsh
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. christopher_walsh@hms.harvard.edu
Chen
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Keating
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Hubbard
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Losey
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Luo
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Marshall
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Miller
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Patel
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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
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