Activities | Families | Sequences | Fold types | References | Help
B6db references: 29551347

type Journal Article
authors Sosio M, Gaspari E, Iorio M, Pessina S, Medema MH, Bernasconi A, Simone M, Maffioli SI, Ebright RH, Donadio S
title Analysis of the Pseudouridimycin Biosynthetic Pathway Provides Insights into the Formation of C-nucleoside Antibiotics
journal Cell Chem Biol
Activity pumg
Family pumg
sel selected
ui 29551347
year (2018)
volume 25
number 5
pages 540-549
keywords C-nucleoside antibiotic; PUM biosynthetic pathway; PUM cluster; PumJ; RNAP inhibitor; TruD-like; amide ligases; pseudouridimycin; pseudouridine synthase; specialized oxidoreductases and aminotransferases
abstract Pseudouridimycin (PUM) is a selective nucleoside-analog inhibitor of bacterial RNA polymerase with activity against Gram-positive and Gram-negative bacteria. PUM, produced by Streptomyces sp. ID38640, consists of a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 5'-aminopseudouridine. We report the characterization of the PUM gene cluster. Bioinformatic analysis and mutational knockouts of pum genes with analysis of accumulated intermediates, define the PUM biosynthetic pathway. The work provides the first biosynthetic pathway of a C-nucleoside antibiotic and reveals three unexpected features: production of free pseudouridine by the dedicated pseudouridine synthase, PumJ; nucleoside activation by specialized oxidoreductases and aminotransferases; and peptide-bond formation by amide ligases. A central role in the PUM biosynthetic pathway is played by the PumJ, which represents a divergent branch within the TruD family of pseudouridine synthases. PumJ-like sequences are associated with diverse gene clusters likely to govern the biosynthesis of different classes of C-nucleoside antibiotics.
last changed 2018/10/04 13:00

B6db references