Biosynthesis of Aurodox, a Type III Secretion System Inhibitor from Streptomyces goldiniensis
Rebecca E. McHugh, John Munnoch, Robyn E Braes, Iain J. W. McKean, Josephine Giard, Andrea Taladriz‐Sender, Frederik Peschke, Glenn A. Burley, Andrew J. Roe, Paul A. Hoskisson
Abstract
Enterohemorrhagic Escherichia coli (EHEC) is a significant global pathogen for which traditional antibiotic treatment is not recommended. Aurodox inhibits the ability of EHEC to establish infection in the host gut through the specific targeting of the type III secretion system while circumventing the induction of toxin production associated with traditional antibiotics. These properties suggest aurodox could be a promising anti-virulence compound for EHEC, which merits further investigation. Here, we characterized the aurodox biosynthetic gene cluster from Streptomyces goldiniensis and established the key enzymatic steps of aurodox biosynthesis that give rise to the unique anti-virulence activity. These data provide the basis for future chemical and genetic approaches to produce aurodox derivatives with increased efficacy and the potential to engineer novel elfamycins.