title: Chemical logic and enzymatic machinery for biological assembly of peptidyl nucleoside antibiotics.
abstract: Peptidyl nucleoside antibiotics are a group of natural products targeting MraY, a bacterial translocase involved in the lipid-linked cycle in peptidoglycan biosynthesis. In this Perspective, we explore how Nature builds complex peptidyl nucleoside antibiotics scaffolds from simple nucleoside and amino acid building blocks. We discuss the current stage of research on biosynthetic pathways for peptidyl nucleoside antibiotics, primarily focusing on chemical logic and enzymatic machinery for uridine transformation and coupling to peptides. We further survey the nonribosomal biosynthetic paradigm for a subgroup of uridyl peptide antibiotics represented by pacidamycins, concluded by diversification opportunities for antibiotic optimization.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, United States. christopher_walsh@hms.harvard.edu
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001419:Bacteria / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011741:Pyrimidine Nucleosides / Q000737:chemistry / Q000378:metabolism; D014166:Transferases / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups); D014529:Uridine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009705:Nucleosides; D010455:Peptides; D011741:Pyrimidine Nucleosides; C049983:capuramycin; C002457:polyoxin; D014166:Transferases; D017855:Transferases (Other Substituted Phosphate Groups); C079803:mraY protein, Bacteria; D014529:Uridine