Gao: 'to me, the fungal genome is a treasure'

Researchers at Rice University's Brown School of Engineering have developed a new way to mine fungal genomes for use in what's considered medically useful compounds. 

The approach, called multiplex base-editing (MBE), was used to lure fungi into producing more natural compounds, including some previously unknown to science, according to a press release.

“To me, the fungal genome is a treasure,” Xue Sherry Gao, a chemical and bimolecular engineer at Rice University, said in the release. “However, under most circumstances, fungi ‘keep to themselves’ in the laboratory and don’t produce the bioactive small molecules we are looking for. In other words, the majority of genes or biosynthetic gene clusters of interest to us are ‘cryptic,’ meaning they do not express their full biosynthetic potential."

Compared to single-gene editing, the MBE platform reduced the research timeline by over 80% in equivalent experimental settings, dropping to about two weeks as opposed to three months, the release stated. The study, published in the Journal of the American Chemical Society, is the first time the technique has been deployed as a tool for mining fungal genomes.

According to the researchers, fungi and other organisms produce bioactive small molecules, such as penicillin, to protect themselves from disease agents. These bioactive natural products (NPs) can be used as drugs or as molecular blueprints for designing new drugs. The Gao lab, at Rice’s Brown School of Engineering, used the MBE technology to induce fungi to produce significantly more natural compounds, including some previously unknown to the scientific community. 

Enabled by the MBE platform, Gao's team can easily delete several of the regulatory genes that restrict the production of bioactive small molecules. "We can observe the synergistic effects of eliminating those factors that make the biosynthetic machinery silent," she said in the release. The research was funded by a five-year National Institutes of Health grant and supported by the Robert A. Welch Foundation.