Researchers at the French National Institute for Agricultural Research (Inra) and Inserm have discovered a new family of bacterial enzymes that can produce hitherto unidentified peptides with antibiotic activity. Published in Nature Chemistry, this work holds promise for the synthesis of molecules of pharmaceutical interest and the design of new antibiotics.
As part of research involving study of the enzymes of the gut microbiota, researchers from Inra and Inserm studied the model bacterium Bacillus subtilis. Genetic analysis of the organism showed the presence of genes conserved by common bacteria from the gut microbiota, such as enterococci. *
The scientists were especially interested in two Bacillus subtilis genes potentially coding for a peptide and an enzyme from the superfamily known as “radical SAM enzymes.” Their work has made it possible to describe a new enzyme mechanism that can transform a peptide into a bioactive molecule. Known as epimerisation, this enzymic transformation brings about a change in the configuration of certain amino acid residues from the L- configuration (normally found in peptides) to the D-configuration. The researchers discovered how this enzyme works: it removes a hydrogen atom from the alpha-carbon atom of the amino acid residues and donates another, bringing about their epimerisation. It is a mechanism not previously described in nature.
It is the first time that researchers have demonstrated the ability of “radical SAM” enzymes to catalyse epimerisation within a peptide in vitro. Surprisingly, the peptide thus modified and called an “epipeptide” is able to inhibit growth of Bacillus subtilis very effectively. These epipeptides thus represent a new class of natural products that might be used to develop new antibiotics against Gram positive bacteria (such as staphylococci, enterococci or streptococci), which are becoming increasingly antibiotic resistant, constituting a major public health problem.
A study sponsored by the AP-HP has shown for the first time that asymptomatic individuals who carry the c9orf72 mutation, which means they are at risk of developing frontotemporal degeneration (FTD) or amyotrophic lateral sclerosis (ALS), experience cognitive, anatomical, and structural changes ...
A research team from Université Paris Descartes, Inserm and Centre Hospitalier Sainte‐Anne, led by Prof. Marie‐Odile Krebs, has shown that patients suffering from psychotic disorders, and exposed in utero to diethylstilbestrol, presented specific epigenetic changes. These changes correspond to genomic regions notably ...
Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis.
Alhosna Benjdia, Alain Guillot, Pauline Ruffié, Jérôme Leprince & Olivier Berteau.
Nature Chemistry, 6 février 2017. doi:10.1038/nchem.2714