A group of University of Illinois researchers, led by Centennial Chair Professor of the Department of Chemical and Biomolecular Engineering Huimin Zhao, has demonstrated the use of an innovative DNA engineering technique to discover potentially valuable functions hidden within bacterial genomes. Their work was reported in a Nature Communications article on December 5, 2013.
The genome of every bacterial species contains genes that can synthesize a diverse arsenal of compounds. These include natural antibiotics, antifungals, and other biochemicals that help the bacteria fight off unfriendly fellow microbes; such compounds are of potentially great medical importance. The genes encoding the enzymes a bacterium needs to create these compounds are often arranged in clusters. Each gene corresponds to one of a set of proteins that work together in a biochemical pathway to create one or a few products.
If a colony of bacteria is producing a biologically active compound, sometimes referred to as a natural product, scientists can isolate it, study its structure and function, and discover its potential uses. Many natural products have already been discovered by screening the compounds produced by different bacterial and other microbial species.
The compounds discovered so far, however, represent a small fraction of those that bacteria are capable of producing.
Bacteria are masters at survival; their genomes represent a set of contingency plans for a wide array of environmental situations. Like a painter laying out a palette with only the colors needed that day, a bacterium will only express the genes and synthesize the compounds that will help it thrive in its current setting. Constant expression of the gene clusters that aren’t useful in a given situation would be energetically wasteful.
This conservation of energy is good for bacteria, but bad for researchers hoping to discover new natural products. This was the challenge that Zhao and colleagues hoped to address when they began their project. “Sequence analysis of bacterial genomes indicates that there are many cryptic or silent pathways that have not been discovered,” Zhao said. ” . . .they need the right signal to turn on expression of the whole gene cluster.”
Several strategies have been employed to trick cells into activating their little-used, “cryptic” gene clusters, such as culturing bacteria in a variety of harsh conditions or inserting sets of genes from one species of bacteria into the genome of another species. These techniques involve labor-intensive trial and error, with no guarantee of success.