With the advent of quick and inexpensive next-generation DNA sequencing technologies, bioinformatic tools can tap into natural products, the main source for current small molecule drugs, such as antibacterial, antiviral, anticancer and immune modulating drugs, to identify potential drug-leads in a process called genome mining. However, isolation and characterization of these small compounds that are produced by biosynthetic machineries is traditionally challenging, as these biosynthetic pathways are typically inactive under laboratory conditions and heterologous expression of these clusters in different strains is time consuming, expensive and may not yield a functional compound.

To tackle these challenges, NTx CEO and co-founder, Dr. Alex Koglin teamed up with his former colleague from Los Alamos National Laboratory and Harvard Medical School, Dr. Matthias Strieker, who is currently a visiting Assistant Professor within the Department of Computer Science and Engineering at the University of Notre Dame.

Dr. Strieker and Dr. Koglin, along with Walter J. Scheirer, the Dennis O. Doughty Associate Professor of Computer Science and Engineering at Notre Dame, developed an algorithm, called DruID (Drug-lead IDentification) that is capable of mining genomic data for natural product encoding gene clusters. Compared to current state-of-the-art bioinformatic tools, DruID offers additional features, such as excluding known natural products by integrating machine-learning capabilities. DruID is capable of accurately predicting the structures of the identified natural product, comparing the predicted structures with known natural products, and excluding non-novel structures from further analyses. In addition, by modeling the 3D structure and screening it against drug target structures, the biological activity of the natural product and its potential use as a drug can be predicted.

DruID allows for more effective drug repurposing, suggests naturally accruing modifications of existing drugs, and suggests novel drug leads. The drug lead can then be developed in-house either by synthesis of the predicted structure, heterologous expression of the biosynthetic cluster, isolation from the naturally producing strain, or with NTx’s proprietary cell-free transcription/translation system NTxpress®.

The concept of DruID’s function has been proven by the identification of two novel antibiotics with a new mechanism of action representing an entirely novel class of antibiotics. These novel compounds are currently being preclinically evaluated against multi-resistant tuberculosis-causing pathogens.

“By combining the power of NTx’s platform with the machine learning capabilities that Dr. Strieker and Professor Scheirer have developed at the University of Notre Dame, we have been able to make significant strides in solving the challenges that have traditionally surrounded drug discovery with natural products,” said Dr. Alex Koglin, co-founder, CEO and CSO of NTx. “I am glad to be collaborating with such an incredible talent in Matthias and am excited about what else we can accomplish together moving forward.”

When asked about the project and its performance, Dr. Matthias Strieker concluded, “I am absolutely thrilled to work with Professor Scheirer and Dr. Koglin on this challenging but highly rewarding project. It is incredible that based on technology we are developing, and predictions we make, new drugs can be found in weeks, synthesized cell-free and evaluated for their biological activity and potential drug-use in a few months.”

To learn more about NTx and its proprietary platform, please visit: https://www.ntxbio.com.

To learn more about the Notre Dame’s Department of Computer Science and Engineering, please visit https://cse.nd.edu/.

About NTx

NTx is a bioinformatics and biomanufacturing company that advances medical products and material sciences with cell-free, innovative biomanufacturing solutions. The company is commercializing its biomanufacturing systems NTxpress®, NTxscribe® and the bioinformatics platform, DruID, for the discovery of natural products. NTx biosynthesis technology, which is built for mRNA and proteins that are made in-vitro, is completely defined as is not dependent on cell lines. Its biomanufacturing processes can easily be scaled to meet fluctuating supply needs so that companies can increase and streamline production as they respond to changing global demands. For more information, please visit: https://www.ntxbio.com.