Monday, September 26, 2022

New biosensor system derived from E. coli bacteria could accelerate drug development

For more affordable, sustainable drug options than we have today, the drugs we take to treat high blood pressure, pain or memory loss may one day come from engineered bacteria, which are cultured in yogurt-like vats. Is. And thanks to a new bacterial tool developed by scientists at the University of Texas at Austin, the process of improving drug manufacturing in bacterial cells may come sooner than we thought.

For decades, researchers have been eyeing ways to make drug manufacturing more affordable and sustainable than current processes from drug makers, many of which rely on plant crops or petroleum. The use of bacteria has been suggested as a good organic alternative, but detecting and optimizing the production of therapeutic molecules is difficult and time-consuming, requiring months. In a new paper this week nature chemical biology, The UT Austin team presents a biosensor system derived from E. coli bacteria that can be adapted to accurately and within hours the detection of all kinds of therapeutic compounds.

We are exploring how to ‘sense’ bacteria, similar to olfactory receptors or taste receptors, and use them to detect the different compounds they can make.”


Andrew Ellington, Professor of Molecular Biology and corresponding author on the paper

Many of the medicines we take are made from ingredients extracted from plants (for example, morphine, the narcotic pain reliever that comes from poppies, or galantamine, a drug treatment for dementia that comes from daffodils). Extracting drugs from these plants is complex and resource-intensive, requiring water and area to grow the crops. Supply chains are easily disrupted. And floods, fires and droughts can damage crops. Achieving similar therapeutic components using synthetic chemistry also brings problems, as the process relies on petroleum and petroleum-based products involving waste and expense.

Enter the humble bacteria, a cheap, efficient and sustainable alternative. The genetic code of bacteria can be easily manipulated to become factories of drug production. Bacteria’s biological systems are used to produce specific molecules as part of a natural cellular process, in a process called biosynthesis. And bacteria can replicate at a high speed. All they need to work is sugar.

Unfortunately, manufacturers have no way to quickly analyze different strains of engineered bacteria to identify those capable of producing the desired drug amounts in commercial quantities; So far. Precisely analyzing thousands of engineered strains on the way to a good manufacturer could take weeks or months with current technology, but only a day with the new biosensor.

“There are currently no biosensors for most plant metabolites,” said Simon d’Olsnitz, a research scientist in the Department of Molecular Biosciences and first author on the paper. “With this technology, it should be possible to create biosensors for a wide range of drugs.”

Biosensors developed by D’Olsnitz, Ellington and their colleagues quickly and accurately determine the amount of a given molecule that a strain of bacteria is producing. The team developed biosensors for a variety of common drugs, such as cough suppressants and vasodilators, which are used to treat muscle spasms. Molecular images of the biosensors, taken by X-ray crystallographers Wonte Kim and Yan JC Zhang, show exactly how they tightly hold their fellow drug. When the drug is detected by the biosensor, it flashes. Additionally, the team engineered their own bacteria to produce a compound found in many FDA-approved drugs and used biosensors to analyze product production, briefly showing how quickly the chemical could be manufactured. How industry can adopt biosensors to adapt to

“Although this is not the first biosensor,” D’Olsnitz said, “this technology allows them to be developed faster and more efficiently. In turn, this opens the door to producing more drugs using biosynthesis.” “

Vante Kim, Nathaniel T. Burkholder, Kamyab Javanmardi, Yan Jesse Zhang and Hal Alper of UT Austin and Ross Thayer, previously from UT Austin and now at Rice University, collaborated on the research. The research was funded by the Defense Advanced Research Projects Agency, The Welch Foundation, the Air Force Office of Scientific Research and the National Institutes of Health. in Molecular Biology near Ellington, Nancy Lee and Perry R. Bass is the Regent Chair.

Source:

University of Texas at Austin

Journal Reference:

D’Olsnitz, S., and others. (2022) Using fungible biosensors to develop improved alkaloid biosynthesis. Nature Chemical Biology. doi.org/10.1038/s41589-022-01072-w.

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