Scientists hijack bacteria to ease drug manufacturing

 

The prescription we use to manage high blood pressure, discomfort, or memory loss may one day come from modified bacteria, cultivated in a vat like yogurt, offering more inexpensive, sustainable therapeutic alternatives than we now have. And sooner than we anticipated, the process of boosting medication manufacture in bacterial cells may be possible owing to a new bacterial tool created by researchers at The University of Texas at Austin.

Researchers have been looking for solutions to reduce the cost and environmental impact of pharmaceutical manufacturers' present procedures, many of which rely on either plant crops or petroleum, for decades. The use of bacteria has been recommended as a suitable organic alternative, but it is challenging and time-consuming to find and optimize the synthesis of medicinal compounds, taking months at a time. The UT Austin team describes a biosensor system built from E. coli bacteria in a new publication published this week in Nature Chemical Biology. This system can be modified to detect various medicinal chemicals precisely and in a matter of hours.

Professor of molecular biosciences and corresponding author of the research Andrew Ellington stated, "We're working out how to give bacteria'senses,' comparable to olfactory receptors or taste receptors, and utilize them for detection of the many substances they could create."

Many of the medications we use are formulated with plant-based components (think, for example, morphine, the narcotic painkiller that comes from poppies, or galantamine, a drug treatment for dementia that comes from daffodils). These plants require water and land to cultivate the crops, making the drug extraction process difficult and resource-intensive. Supply chains are prone to interruption. Additionally, drought, fire, and floods may all harm crops. Synthetic chemistry used to create comparable medicinal components has its own set of issues because it depends on wasteful petroleum and petroleum-based goods.

Here's a simple, cost-effective, and sustainable replacement: bacteria. It is simple to alter bacteria's genetic material so that they may be used as medication manufacturing plants. The biological systems of the bacteria are used in a procedure known as biosynthesis to manufacture certain chemicals as a byproduct of the cellular activity. And microorganisms have a rapid rate of replication. They only need sugar to do the task.

Until recently, however, there hasn't been a straightforward way for manufacturers to compare several strains of altered bacteria to determine which ones can produce a particular medication in large enough numbers for commercial use. With present technology, it can take weeks or months to accurately analyze the hundreds of modified strains that are on route to a good producer, but the new biosensors can do it in just one day.

According to Simon d'Oelsnitz, a research scientist at the Department of Molecular Biosciences and the paper's primary author, "there are currently no biosensors for the majority of plant metabolites." This method should make it easy to develop biosensors for a variety of medications.

The biosensors created by d'Oelsnitz, Ellington, and coworkers quickly and precisely estimate how much of a certain chemical a particular bacterial strain is generating. The group created biosensors for a number of popular medications, including vasodilators and cough suppressants, which are used to alleviate muscular spasms. Wantae Kim and Yan Jessie Zhang, X-ray crystallographers, captured molecular pictures of the biosensors to demonstrate how strongly they bind to their companion medication. The medication glows when the biosensor picks it up. The scientists also built their own bacteria to generate a substance that can be found in a number of FDA-approved pharmaceuticals while using biosensors to monitor product production, thus demonstrating how industry may swiftly embrace biosensors to optimize chemical manufacturing.

"Although not the first biosensor, according to d'Oelsnitz, "this approach makes it possible for them to be created more quickly and effectively. This in turn makes it possible to create additional medications through biosynthesis."