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Collaborative team discovers new natural products, to be used as sources of antibiotics, at unprecedented speed

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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.
October 18, 2022

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.

However, Doug Mitchell (MMG), the John and Margaret Witt Professor of Chemistry at University of Illinois, says this pales in comparison to the number of compounds these organisms have the capacity to make using the genetic pathways they possess.
“This is just the tip of the iceberg,” said Mitchell. “There’s a disparity in what we know today in terms of known molecules versus what nature has the capacity to produce. Like 100 to one at least.”
One group of natural products that has become a popular source of antibiotics is called ribosomally synthesized and post-translationally modified peptides, or simply, “RiPPs.” Traditional methods for accessing RiPPs are slow, and involve taking genes one by one and putting them into a model organism, like E. coli, to see what compound it produces.
However, in a new paper resulting from a massive collaborative effort at the Carl R. Woese Institute for Genomic Biology, researchers were able to discover and characterize new RiPPs at an unprecedented speed and scale using the Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB). This is a laboratory automation system that can evaluate and assemble multiple synthetic gene pathways from hundreds of genes at once, something that would traditionally take many researchers and much more time to accomplish.
The project features a collaboration between Mitchell’s lab, the lab of Huimin Zhao (BSD/GSE leader/CABBI/CGD/MMG), the Steven L.

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