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Orthoformimycin, a Selective Inhibitor of Bacterial Translation Elongation from Streptomyces Containing an Unusual Orthoformate
journal contribution
posted on 2013-09-20, 00:00 authored by Sonia I. Maffioli, Attilio Fabbretti, Letizia Brandi, Andreas Savelsbergh, Paolo Monciardini, Monica Abbondi, Rossana Rossi, Stefano Donadio, Claudio O. GualerziUpon 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.
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functionorthoformate moietymRNA30 Stranslation elongationpolypeptide productsOrthoformimycinextractantibioticorthoformimycininhibitionnovel classfluorescence50 S subunittranslocationStreptomyces Containingtranslation inhibitorsmoleculeefficiencycompoundthroughput screeningUnusual OrthoformateUponspectroscopic methodsflow kineticsBacterial Translation Elongationanalysislengthchemicalprotein synthesisSelective Inhibitor
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