title: Orthoformimycin, a selective inhibitor of bacterial translation elongation from Streptomyces containing an unusual orthoformate.
abstract: Upon high throughput screening of 6700 microbial fermentation extracts, we discovered a compound, designated orthoformimycin, capable of inhibiting protein synthesis in vitro with high efficiency. The molecule, whose structure was elucidated by chemical, spectrometric, and spectroscopic methods, contains an unusual orthoformate moiety (hence the name) and belongs to a novel class of translation inhibitors. This antibiotic does not affect any function of the 30S ribosomal subunit but binds to the 50S subunit causing inhibition of translation elongation and yielding polypeptide products of reduced length. Analysis by fluorescence stopped flow kinetics revealed that EF-G-dependent mRNA translocation is inhibited by orthoformimycin, whereas, surprisingly, translocation of the aminoacyl-tRNA seems to be unaffected.
authors.affiliation: NAICONS , 20138 Milano, Italy.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Maffioli
authors.forename: Attilio
authors.initials: A
authors.lastname: Fabbretti
authors.forename: Letizia
authors.initials: L
authors.lastname: Brandi
authors.forename: Andreas
authors.initials: A
authors.lastname: Savelsbergh
authors.forename: Paolo
authors.initials: P
authors.lastname: Monciardini
authors.forename: Monica
authors.initials: M
authors.lastname: Abbondi
authors.forename: Rossana
authors.initials: R
authors.lastname: Rossi
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
authors.forename: Claudio O
authors.initials: CO
authors.lastname: Gualerzi
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D055808:Drug Discovery; D005561:Formates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005658:Fungi / Q000737:chemistry*; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D020653:Peptide Elongation Factor G / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D013302:Streptomyces / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005561:Formates; D020653:Peptide Elongation Factor G; C587522:orthoformimycin; C030544:formic acid