Emily P. Balskus
Chemical Discovery in Microorganisms
The focus of our research is the discovery of new enzymatic and non-enzymatic chemistry in living systems. We are particularly inspired by the breadth of reactions used by microorganisms in both primary and secondary metabolism. Microbes are Nature’s synthetic chemists, continually evolving elegant chemical solutions for problems inherent to their growth and survival in diverse environments. Understanding microbial chemistry is important; in addition to playing significant roles in the ecology of producing organisms, small molecules made and manipulated by bacteria and fungi have medicinal and industrial applications. The emerging field of synthetic biology has also fueled interest in engineering microbial metabolism to produce small molecules of natural and non-natural origins; such efforts will greatly benefit from the ability to introduce new chemistry, both enzymatic and non-enzymatic, into designed pathways.
One area of interest is the discovery of new biosynthetic pathways and enzymes using a genome mining approach heavily influenced by our deep understanding of chemical reactivity. We are targeting pathways from both primary and secondary microbial metabolism. Particular areas of interest include uncovering biosynthetic pathways for natural products of unusual molecular architecture that may be assembled using novel enzymatic chemistry and characterizing metabolic pathways from the gut microbiota that may influence various aspects of human health.
A second focus of the lab is studying enzymatic transformations involved in the synthesis of biologically active cryptic natural products, secondary metabolites whose genetic basis of biosynthesis are known but whose chemical structures are unidentified. We have chosen to focus on a subset of these metabolites that have important biological activity. By combining bioinformatic analysis and in silico structure prediction with synthetic chemistry and enzyme characterization, we hope to test structural hypotheses and ultimately achieve structure determination and/or synthesis of these fascinating molecules.
Finally, we are investigating whether it is possible to chemically modify small molecules in the presence of microorganisms using methods and design principles from synthetic chemistry. Our long-term goals in this area are to unite the fields of synthetic and biological chemistry by developing catalysts capable of carrying out chemical reactions on cellular metabolites and to gain a better understanding of how chemical alteration of metabolites impacts the physiology of producing organisms. Ultimately, we will apply our methods to address problems in the areas of synthetic biology and medicine.