1/2015

Biotechnology speeds up drug development

Discovering and developing a new drug may take 20 years and cost a fortune. Researchers at TUT are attempting to turn bacteria, fungi and other microbes into biofactories to accelerate the process.

Robert Franzen ja Matti Karp

 

Professor of Organic Chemistry Robert Franzén and Professor of Bioengineering Matti Karp say that advances in biotechnology and bioinformatics hold great promise for the future treatment of, for example, malaria. The bioactivity of organic molecules is one of the areas of interest for researchers in the Department of Chemistry and Bioengineering.

 

“Conventional drug development processes are tremendously expensive and time consuming. Pharmaceutical companies may devote an average of 20 years and more than EUR 300 million to bring a new drug to market. They have only 20 years to recoup their R&D costs before their patent expires. That’s why we need more effective drug development processes,” says Robert Franzén, Professor of Organic Chemistry in the Department of Chemistry and Bioengineering.

There are more than 60,000 molecules that are known to have medicinal properties, and yet only 150―200 drugs that are new chemical entities are registered on an annual basis. However, a substantially larger number of generic drugs, most of which are simple derivatives of existing drugs, enter the market each year.

Computer-aided drug design, high-throughput screening and, increasingly, biotechnological methods are used to enhance and speed up drug development.

Long and complex synthesis routes

“Drugs are traditionally synthesized in a laboratory. The production of complex organic compounds is an arduous process that may include up to 20―30 phases and take a great deal of time,” Franzén says.

The synthesis of the widely used pain killer Aspirin starts with ethylene, which is converted into acetaldehyde and then into acetic anhydride, salicylic acid and finally acetylsalicylic acid. The process is simple and requires no biotechnological methods. The situation is quite different, if the molecule is more complex and intended to elicit an intricate therapeutic response.

“This is where biotechnology can lend a hand by speeding up the synthesis process and producing new drug candidates that can be chemically modified. This way the production process doesn’t have to start from scratch. Biotechnological methods could also help remove current bottlenecks in drug discovery, if conventional synthetic processes are not giving the intended results.”

Microbes as miniature factories

The world’s first natural antibiotic, penicillin, was accidentally discovered by Alexander Fleming when he noticed that bacterial growth was suppressed in a circle around a spot of mould. The discovery earned him the Nobel Prize in 1945. Since then, different species of moulds have been used in the production of antibiotics.

“Antibiotics and penicillin-like organic molecules are grown in industrial fermenters that hold anything between a few hundred and 100,000 litres of nutrient solution. A biotechnological technique exploiting bacteria or moulds allows the process to be scaled up to industrial proportions,” Professor of Bioengineering Matti Karp says.

When microbes are isolated from natural products, the yield of medically valuable molecules is initially low. But as Karp says, microbes can be turned into highly effective biofactories by modifying their metabolism.

E. coli – the workhorse of molecular biologists

Bioinformatics is another field that is contributing to the development of new drugs. The volume of genomic data derived from tissue samples and microbes is growing exponentially. With the cost of determining a person’s complete genetic blueprint plummeting, advances in bioinformatics are transforming the way new drugs are developed.

“Now that we’re able to compare the genomes of different microbes, we can select certain genes of organisms, whose genomes have been completely sequenced, to be used as platforms for the production of organic molecules. Escherichia coli is usually the first host of choice. It has long been the standard laboratory workhorse,” Karp describes.

Advances in biotechnology and bioinformatics hold great promise in our ability to treat, for example, malaria. According to Karp, exciting new applications are already on the horizon. Biotechnology has already made possible the synthesis of artemisin, an expensive antimalarial drug extracted from trees. It is a potential lifesaver for millions of poor people who are living in tropical countries and are infected with malaria.

New drugs from Finnish forests?

Pine

 

Plants continue to provide a valuable source of pharmaceutically important bioactive compounds.

 

Plants have been used in folk medicine throughout human history. They continue to provide a valuable source of pharmaceutically important bioactive compounds. Approximately one-fourth of prescription drugs used today come directly from or are derivatives of plants.

“Still, only a small percentage of the world’s known plant species have been photochemically analysed for their medicinal potential,” says MSc (Tech) Jenni Tienaho of the Department of Chemistry and Bioengineering.

Fungi, needles, tree stumps and bark

Tienaho’s master’s thesis explores bioactive compounds isolated from fungi, pine and spruce trees growing in Finnish forests. The thesis was written in collaboration with the Finnish Forest Research Institute (METLA), which is now part of the Natural Resources Institute in Finland. The approach is unique: this is the first time that biosensors are used to analyse the bioactivity of forest-based extracts.

“I used biosensors based on bacteria and yeast cells that were genetically modified to light up in the presence of specific bioactive compounds. I discovered these compounds in fungi growing inside the roots of pines, in the stumps and needles of pines and the inner bark of spruces,” Tienaho says.

Fungal, pine and spruce extracts demonstrate antioxidant properties, meaning that they prevent oxidation. In addition, they have antimicrobial properties that damage bacterial DNA.

“The goal of my dissertation will be to detect compounds that give rise to these bioactive properties and thereby identify potential new drug leads.”

 

Text: Leena Koskenlaakso
Photo: Mika Kanerva and Petri Laitinen

 
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