March 26, 2009

Antibiotic thiostrepton genes identified

U.S. scientists say they've identified the genetic machinery responsible for synthesizing thiostrepton, a powerful antibiotic produced by certain bacteria.

Georgia Institute of Technology Assistant Professor Wendy Kelly, postdoctoral fellow Chaoxuan Li and graduate student Lisa Pan said the antibiotic, although effective against the methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, thiostrepton has only limited applications in humans because it is not water soluble.

The scientists said their identification of the gene cluster responsible for producing thiostrepton could make the drug more useful by improving its water solubility.

Beyond possible medical applications, the researchers said their discovery produced a scientific surprise: Thiostrepton is derived from a genetically encoded peptide that undergoes no fewer than 19 modifications. That makes it one of the most complex such processes known.

We are interested in making derivatives of this peptide drug that retain their potency and are efficiently processed by biochemical machinery, said Kelly. We want to put in substitutions to the genetic machinery that may create a more water soluble analog and could potentially be used for development of a new class of antibacterial agent.

Details of the work were published online in the March 5 issue of the Journal of the American Chemical Society.