Our primary objective is to use a blend of chemical and biological approaches to address the alarming rise in antibiotic resistance. In this endeavour, we seek to identify and characterize novel antibiotic compounds. Our approach involves genome-mining, isolation and characterization of novel natural products, and mechanistic studies of key natural product biosynthetic enzymes. Taken together, our approach aims to expedite the discovery of future medicines from biological sources. Of special interest are compounds that only kill pathogenic bacteria or directly target mechanisms of virulence. Unlike currently deployed antibiotics, which exclusively target essential life processes, our strategy holds great potential in delaying resistance. The Mitchell laboratory is a multidisciplinary team that draws methodology from the fields of chemical biology, organic chemistry, microbiology, pharmacology, structural biology, and bioinformatics.
Nilkamal and Graham have published a perspective in Biochemistry that summarizes advances made in the past 10 years for how radical SAM enzymes are utilized in RiPP biosynthesis.
Nilkamal has published a paper in eLife. Nilkamal, along with collaborators in the Metcalf lab, has published a paper that shows a TfuA-associated YcaO thioamides MCR, a methane-producing enzyme.
Congratulations to Chris on his successful thesis defense!
Doug will be speaking at the Natural Product Discovery and Development in the Genomic Era Conference, which will be held in Clearwater, FL from Jan. 21-24, 2018.
Brandon Burkhart and Graham Hudson, along with collaborators from the van der Donk lab, published a paper in ACS Cent. Sci. This work established a new method for rationally designing RiPP pathways based on chimeric leader peptides. A cyclodehydratase was combined with enzymes from the lanthipeptide and sactipeptide RiPP classes to make novel hybrid RiPP structures, Overall, this approach lays a foundation for future RiPP engineering.