Cottrell Scholar Awards - 2015
Chemically-Guided Enzyme Discovery: An Approach to Identifying New Biological Reactions and a Tool for Inspiring Future Scientists
Enzymes – tiny bits of protein -- provide the keys to all kinds of biological processes. They act as catalysts that convert one type of molecule into something different. Without them, life would not exist. Furthermore, it is likely that if we can find or create new and novel enzymes, we will have new tools to modify, and perhaps improve, existing biological processes.
Emily P. Balskus, assistant professor of chemistry and chemical biology, Harvard University, has received Cottrell Scholar funding to look for such enzymes. Her work is taking advantage of increasingly plentiful genome sequencing data, as she develops methods to rapidly link DNA sequences to important biochemical functions among enzymes found in microorganisms, earth’s most abundant life form.
“The rate of data gathering has far outpaced our ability to interpret the functions these data encode,” Balskus said. “This gap is limiting the pace at which we can discover novel enzymes that could greatly enable chemical synthesis.” If this project is successful – although there are no guarantees in fundamental research such as this – it could greatly speed up developments in the rapidly growing fields of metabolic engineering and synthetic biology.
Specifically, Balskus and her research group are focusing on discovering and understanding biosynthetic pathways that microorganisms use to produce natural products with unique structural features.
“We hypothesize that such metabolites are likely assembled using new enzymatic chemistry,” she said. “We have identified a natural product family, the cylindrocyclophanes, which contains unusual carbon–carbon (C–C) linkages [that is, single bonds between two carbon atoms] whose assembly cannot be rationalized using known biochemistry.”
Balskus said that understanding and controlling C–C bond formation is a central challenge of organic chemistry, “because this type of reactivity allows for the generation of larger, complex molecules from simpler building blocks.” Thus, discovery of new C–C bond-forming enzymes would have a large impact on the future creation of biologically useful chemicals.
Balskus is also using some of her Cottrell Scholar funding to create a freshman laboratory course entitled “Discovering Chemistry from the Human Microbiota.” Participating students work with members of her lab to screen a metagenomic library constructed from gut microbial DNA, looking for new genes that give rise to biochemical functions related to the microbiota’s impact on human food and drug metabolism.
“This course is intended to promote careers in science by introducing first-year undergraduates to the thrill of research at a critical time in their academic training,” she said.