New Method of DNA Editing Allows Synthetic Biologists to Unlock Secrets of a Bacterial Genome

A group 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.

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."

Zhao's group, rather than attempting to manipulate the environment, focused on reprogramming the control of gene expression within the cell. They used a genetic engineering method previously developed by Zhao's laboratory, called DNA assembler, to insert small sections of DNA between each gene in a cryptic gene cluster. The sections of DNA added were promoters, specialized regions that help control when and how much nearby genes are expressed. By adding the right promoters, Zhao and colleagues forced the cell to increase expression of every gene in the cluster.