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UID:20251108T222811EST-7836Dl7Iir@132.216.98.100
DTSTAMP:20251109T032811Z
DESCRIPTION:Abstract:\n\nThe emergence of multi-drug resistant organisms cl
 inically presents major challenges to managing human health and threaten t
 he great progress that has been made in preventing morbidity and mortality
  in the age of antibiotics. In order to combat these pathogens\, new antib
 iotics with diverse mechanisms of action will be required. Armeniaspirols 
 represent a novel class of natural product-based antibiotic molecules with
  unknown mechanisms of action. In this talk we will disclose the mechanism
  of action of armeniaspirol. Using total synthesis\, analogs of armeniaspi
 rol were synthesized and their antibiotic properties examined. A combinati
 on of chemoproteomics\, quantitative proteomics\, and a battery of functio
 nal assays were used to discover that aremeniaspirols directly inhibit the
  AAA+ proteases ClpYQ and ClpXP\, leading to dysregulation of the divisome
  and ultimately antibiotic activity. Our in vitro biochemical results were
  validated by in vivo by comparisons with genetic knockouts. Sub-lethal an
 tibiotic challenges further suggested that resistance to aremiaspirol inhi
 bition of ClpYQ and ClpXP is difficult to achieve without catastrophic con
 sequences for the bacteria. Lastly\, we show through characterization of t
 he armeniaspirol biosynthetic pathway that an advanced though structurally
  distinct biosynthetic precursor is also highly antibiotic. Intriguingly\,
  it inhibits a different target providing a snapshot of how complex biosyn
 thetic pathways may evolve. The armeniaspirols thus represent an important
  new tool to combat multi-drug resistance\, through a potent and highly no
 vel mechanism of action and provide a rich avenue for studying the evoluti
 on of complex bioactive natural products.\n\nBio:\n\nChristopher Boddy is 
 a professor in the Chemistry and Biomolecular Sciecnes department at the U
 niversity of Ottawa and the director of the Biochemistry program. Through 
 his PhD with KC Nicolaou in synthetic organic chemistry\, he developed a l
 ove of complex bioactive natural products\, which was only deepened by stu
 dying natural product biosynthesis with Chaitan Khosla. His research progr
 am at the interface of chemistry\, biology\, and microbiology focuses on t
 he synthesis\, biosynthesis\, and function of complex polyketide and non-r
 ibosomal peptide natural products.\n
DTSTART:20200310T170000Z
DTEND:20200310T183000Z
LOCATION:Room 10\, Maass Chemistry Building\, CA\, QC\, Montreal\, H3A 0B8\
 , 801 rue Sherbrooke Ouest
SUMMARY:Chemical Society Seminar: Christopher Boddy - Biosynthesis\, synthe
 sis\, and mechanism of action of the armeniaspirol antibiotics
URL:/chemistry/channels/event/chemical-society-seminar
 -christopher-boddy-biosynthesis-synthesis-and-mechanism-action-armeniaspir
 ol-303032
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