from genes to molecules

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.

outsmarting bacteria since 2009»

Plantazolicin, a genetically-encoded molecule

recent news

Lonnie has published a chapter in Methods in Enzymology describing the use of reactivity-based screening for the discovery of natural products with specific functional groups.

Sangeetha, Lonnie, and former members Xiaorui, Adam, and Bryce, along with collaborators in the Pogorelov lab, published a paper in ACS Chem. Biol. where they report an update to RODEO featuring a graspetide-specific precursor peptide scoring module.

Yuanyuan, Ashley and Laura published a paper in J. Am. Chem. Soc. that used cell-free biosynthesis (CFB) to rapidly generate lasso peptide variants and evaluate the substrate tolerance of the biosynthetic pathway.

Congrats to Adam for passing his PhD thesis defense and good luck to him as he continues his scientific career at Merck!

Former members Andi and Nilkamal have published a chapter in Methods in Enzymology detailing methods used for the investigation of peptide backbone thioamides installed by YcaO enzymes.


Tim and collaborators in the Gerlt lab published a paper in ACS Bio Med Chem Au which describes a new web-based resource: The genomic enzymology portal compiles and classifies all salient information on the sequence-function space of radical SAM enzymes, one of the largest and most diverse enzyme superfamilies known. We anticipate this tool will aid in the discovery of new enzyme chemistry.