Of all the drugs used in a hospital to treat patients, about 75% are secondary metabolite or secondary metabolite-derived molecules. My lab is interested in all aspects of these metabolites, ranging from their biosynthesis and their microbiological role in nature to applications in the clinic.
Secondary Metabolism in Escherichia coli
E. coli is a Gram-negative bacterium most well known for diarrheal diseases, but some strains have been used as probiotic or even as therapy against other bacteria. One such strain is E. coli Nissle 1917. The biosynthesis of secondary metabolites is crucial in its ability to outcompete pathogenic bacteria in the gut environment. We identified an aryl polyene biosynthetic gene cluster in the genome of E. coli Nissle 1917 and characterized its biosynthesis [Jones et al. 2021]. A different secondary metabolite, colibactin, appeared to be crucial in competition with Vibrio cholerae, as shown in a collaborative project with the Zhu lab at UPenn [Chen et al. 2022].
Biosynthetic gene cluster of an aryl polyene (APE) produced by E. coli Nissle 1917.
Mass Spectrometry
Our lab uses liquid chromatography mass spectrometry on a Waters Synapt G2Si HDMS QTOF equipped with an Acquity i-class UPLC to do targeted and untargeted metabolomics and lipidomics. We also do basic proteomics (intact protein, digested protein), and our system is equipped with a DESI imaging mass spectrometry unit for 2D mass spectrometry.
Vitamin Biosynthesis
Dr. Amy T. Ma spearheaded a project centered around the biosynthesis of cobamides, including vitamin B12. Cobamides are essential co-factors produced by prokaryotes, that need to be crossed between bacterial species since only some produce them, but most need them. We are deciphering crosstalk, enzymatic activities and presence of diverse cobamides in complex microbiomes (gut, soil, water, fecal samples, etc.).