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Radical-SAM enzyme TsrM catalyzes the reaction that produces Thiostrepton A. © INRA

Researchers reveal complex mechanism used by bacteria to synthesize antibiotics

Bacteria use hitherto-undescribed pathways and a newly discovered enzyme family to synthesize complex antibiotics from simple amino acids. These are the surprising results of a collaborative study recently published in Nature Communications that was carried out by INRA researchers and their colleagues at the University of Michigan.This discovery has pharmacological implications, namely because it could help scientists design new antibiotics.

Updated on 10/27/2015
Published on 10/12/2015

Thiostrepton A is an antibiotic naturally produced by Streptomyces bacteria that was discovered in the 1950s. The compound may also help in the fight against cancer because it inhibits proto-oncogenes, genes that can promote the proliferation of cancerous cells. However, until very recently, its synthesis remained a mystery. It was only known that bacteria used two simple precursors, one being the amino acid tryptophan, to produce the complex Thiostrepton A molecule.

Over the last several years, INRA researchers have been studying the role played by the newly described radical-SAM family of enzymes. One member of this family, TsrM, is involved in a crucial early stage of Thiostrepton A biosynthesis. In a new study coauthored with collaborators from the University of Michigan, INRA scientists have finally revealed how TsrM transforms tryptophan into Thiostrepton A.

This finding has broad implications. Recent genomic and metagenomic research has shown that radical-SAM enzymes are found throughout the living world and, more specifically, are involved in the synthesis of a variety of antibiotics. Consequently, the results of this study could help guide the development of new medicinal compounds, especially novel antibiotics. Furthermore, this study sheds new light on the functions of a large number of enzymes, including some that are expressed by intestinal microbiota (e.g., the bacteria found in the human digestive tract) whose roles remain uncharacterized.

Contact(s)
Scientific contact(s):

  • Olivier Berteau (33 (0)1 34 65 23 08) Joint Research Unit for Food and Gut Microbiology for Human Health
Press Relations:
INRA News Office (33 (0)1 42 75 91 86)
Associated Division(s):
Microbiology and the Food Chain , Nutrition, Chemical Food Safety and Consumer Behaviour
Associated Centre(s):
Jouy-en-Josas

Reference

Alhosna Benjdia, Stéphane Pierre, Carmen Gherasim, Alain Guillot, Manon Carmona, Patricia Amara, Ruma Banerjee & Olivier Berteau. The thiostrepton A tryptophan methyltransferase TsrM catalyses a cob(II)alamin-dependent methyl transfer reaction. Nature Communications, 12 October 2015. 
DOI: 10.1038/NCOMMS9377