Home Career Scientists hijack bacteria to facilitate drug production — ScienceDaily

Scientists hijack bacteria to facilitate drug production — ScienceDaily


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 bacteria cultivated in a vat like yogurt. And thanks to a new bacterial tool developed by scientists at the University of Texas at Austin, the process of improving drug production in bacterial cells may begin sooner than we thought.

For decades, researchers have been looking for ways to make drug production more affordable and sustainable than the current processes of pharmaceutical manufacturers, many of which depend on either crops or oil. The use of bacteria has been proposed as a good organic alternative, but the discovery and optimization of the production of therapeutic molecules is complex and time-consuming, requiring months on end. In a new newspaper published this week in Nature Chemical biology, team at UT Austin presents a biosensor system derived from Escherichia coli bacteria that can be adapted to accurately detect all kinds of therapeutic compounds in a matter of hours.

“We’re figuring out how to give bacteria ‘senses’ similar to olfactory and taste receptors and use them to detect the different compounds they can form,” said Andrew Ellington, professor of molecular biological sciences and corresponding author on the paper.

Many of the medicines we take are made from ingredients derived from plants (think, for example, morphine, a narcotic pain reliever derived from the poppy, or galantamine, a dementia drug derived from daffodils). Extracting medicines from these plants is difficult and resource-intensive, requiring water and acreage for growing crops. Supply chains are easily disrupted. And crops can suffer from floods, fires and drought. Obtaining similar therapeutic compounds using synthetic chemistry is also problematic, as the process is dependent on petroleum and petroleum-based products, associated with waste and costs.

Enter the humble bacteria, a cheap, effective and sustainable alternative. The genetic code of bacteria can be easily manipulated to become drug factories. In a process called biosynthesis, the biological systems of bacteria are used to produce certain molecules as part of a natural cellular process. And bacteria can reproduce at a high rate. All they need to work is sugar.

Unfortunately, until now, manufacturers have not had the ability to quickly analyze different strains of engineered bacteria to identify those capable of producing the right amounts of drugs on a commercial scale. Accurately analyzing thousands of engineered strains en route to a good producer can take weeks or months with current technology, but only a day with new biosensors.

“There are currently no biosensors for most plant metabolites,” said Simon d’Elsnitz, a research associate in the Department of Molecular Biological Sciences and first author of the paper. “With this technique, it should be possible to create biosensors for a wide range of drugs.”

The biosensors developed by d’Oelsnitz, Ellington and their colleagues quickly and accurately determine the amount of a given molecule produced by a strain of bacteria. The team developed biosensors for several types of common drugs, such as cough suppressants and vasodilators used to treat muscle spasms. Molecular snapshots of the biosensors, taken by X-ray crystallographers Wangtae Kim and Yan Jessie Zhang, show exactly how they tightly grip their partner’s drug. When the drug is detected by the biosensor, it glows. Additionally, the team engineered their own bacteria to produce a compound found in several FDA-approved drugs and used biosensors to analyze product yield, essentially showing how industry can adopt biosensors to rapidly optimize chemical production.

“Although not the first biosensor,” d’Elsnitz said, “this technique allows us to develop them faster and more efficiently. In turn, this opens up the possibility of producing more drugs through biosynthesis.”

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Materials is provided University of Texas at Austin. Note: Content can be edited for style and length.

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