Mining microbial genomes to discover natural products

The world around us contains many chemicals that are useful for medicines, crop protection, and animal health. These chemicals—known as natural products—have typically been discovered by sheer luck. Unsurprisingly, traditional techniques often find the same products, like antibiotics, repeatedly thus creating a need for new technologies. To address this growing demand, William Metcalf (MMG leader), a professor of microbiology, co-founded the company MicroMGx in 2015.

“A large number of antibiotics, herbicides, pesticides, and animal health medicines are derived from natural products. However, the biggest issue is rediscovery of the same compounds over and over again,” Metcalf said. Along with Neil Kelleher, a professor at Northwestern University, Metcalf had been working on the idea of a new discovery platform for a long time. The project got a boost when James Doroghazi, who was a postdoctoral fellow at the IGB, did much of the early work. The company grew out of a proof-of-concept award at the IGB in 2012.

Together with Kelleher and Regan Thomson, also a professor at Northwestern University, Metcalf co-founded the company Microbial Pharmaceuticals. Later the name was changed to MicroMGx, an acronym for microbial metabologenomics. The company’s first employee was Anthony Goering, who discovered the first novel compound using MicroMGx’s technology platform.

“MicroMGx is working to lower the barriers for accessing natural products,” Goering said. “Once we do that, it will greatly expand how we can use natural products to make a difference.”

MicroMGx combines information from two sources: genes that are involved in the biosynthesis of natural products, and mass spectrometry data that show what molecules are produced by microorganisms. “We can pick out which molecules are valuable and have activities that are useful to human beings. At the same time, we can link those molecules to the genes that are responsible for their production. This allows us to enhance the production or make derivatives that may have different activities,” Metcalf said.

“The platform was built to work with any bacteria. We work with soil bacteria that we’ve obtained from friends and family from around the country. So far, we’ve isolated 3500 unique bacteria for analysis with our platform, and have already published seven papers, each of which has a novel natural product,” said Jack Kloeber, the CEO of MicroMGx. The company’s scientists have also worked with fungi and have isolated 200 of them so far. “We have only scratched the surface of what valuable chemicals we can discover from these microbes,” Kloeber said.

The company’s platform can potentially discover hundreds of natural products that may be useful for different applications, increasing their ability to collaborate with other companies. MicroMGx currently partners with Corteva, an agricultural chemical company, and Elanco, a pharmaceutical company that produces medicines for animal health.  The company has also recently been chosen as one of 6 finalists in the UPL-Radicle Challenge, out of 160 qualified entrants. The mission is to scale up innovative agricultural technologies with a focus on soil health, crop resilience, and reducing agriculture’s carbon footprint.

“Because our platform’s potential is too big for one company to do all the product development, we will create a stream of new molecules and collaborate with many companies,” Kloeber said. “It’s exciting because this small company could change the speed and cost of discovery in multiple life science industries. Very few pharmaceutical companies are looking at natural products right now. By giving them access to all the ones we find, we have a chance to place many useful products on the market.”

“I love this work and I would do it solely for the science,” Metcalf said. “But I love the idea that doing what you love can lead to the discovery of something that could help people. This science has the potential to solve big problems for society and that makes it all the more gratifying,”

The other members of MicroMGx include Rajmony Pannu, Gini Besant, Jason Pillai, Andrew Sutter, Jennifer Kelleher, and Jayaram Pazhanikumar. Pannu is an angel investor who also serves as one of the Directors. He brings pharmaceutical and entrepreneurial expertise to the company’s decision making.