natural products

Living organisms produce a myriad of natural products which can be used in modern medicine and therapeutics. Bacteria and other microbes have become the main source for natural products, including a growing family called ribosomally synthesized and post-translationally modified peptides, or RiPPs. The labs of Douglas Mitchell (MMG), John and Margaret Witt Professor of Chemistry, and Huimin Zhao (CABBI/BSD/GSE/MMG), Steven L.

Many of the drugs we utilize in modern medicine are naturally produced by microbes. Penicillin, an antibiotic derived from certain molds, is one of the most notable natural products due to its recognition as one of the biggest advances in medicine and human health. As DNA sequencing has become cheaper and faster, scientists now have access to hundreds of thousands of microbial genomes and the natural products they produce.

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.

Microorganisms possess natural product biosynthetic gene clusters (BGCs) that may harbor unique bioactivities for use in drug development and agricultural applications. However, many uncharacterized microbial BGCs remain inaccessible. Researchers at Illinois previously demonstrated a technique using transcription factor decoys to activate large, silent BGCs in bacteria to aid in natural product discovery.

The mid-20th century was the golden age of natural product discovery. Scientists discovered groundbreaking drugs, like penicillin and tetracycline, from sources in nature.

But as the search for natural products continued, pharmaceutical companies kept finding the same products over and over again. By the early 2000s, most of these companies shut down their natural product discovery programs.

­Nature contains a treasure trove of substances that could help fight human disease. Just this year, the Nobel Prize in Physiology or Medicine honored the development of drugs that fight parasites and malaria based on such “natural products.” But finding these molecules and discovering new chemical identities represents slow and painstaking work. This week in ACS Central Science, researchers report a new way to greatly speed up that process.

It took two postdoctoral researchers, a lab technician, four undergraduates and their faculty advisors only four years – a blink of an eye in pharmaceutical terms – to scour a collection of 10,000 bacterial strains and isolate the genes responsible for making 19 unique, previously unknown phosphonate natural products, researchers report. Each of these products is a potential new drug. One of them has already been identified as an antibiotic.