A new study led by researchers at The University of Texas at Austin revealed a chemical trick in molds that can provide important clues for the field of drug development. The study was published in the journal Nature and is entitled “Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme.”
Some medical therapies to fight cancer, bacterial infections, and the malaria parasite like Artemisinin (a malaria-fighting compound), require a chemical reaction with oxygen to work. More specifically, the introduction of two consecutive oxygen atoms in a compound has been shown to improve their action. However, oxygen radicals are usually harmful and unstable, and the mechanism behind the chemical reaction of inserting two atoms of oxygen at the same time is not fully understood.
Now, researchers discovered a protein in a common mold species (Aspergillus fumigatus) that is able to insert two oxygen atoms into a toxin produced by the mold. This protein, called fumitremorgin B endoperoxidase (FtmOx1), belongs to a family of proteins that can also be found in humans and is known to be involved in several key biological processes such as fatty acid metabolism and gene regulation. The team believes that the human counterpart of mold FtmOx1 enzyme might also be able to perform this complex oxidative reaction.
“Understanding the mechanism is important for drug discovery,” said the study’s primary investigator, Dr. Yan Jessie Zhang, an associate professor of molecular biosciences at The University of Texas at Austin, in a press release. “You don’t want to develop a drug based on a reaction mechanism that is totally wrong and find out later that the biosynthetic strategy doesn’t work.”
The research team hopes that its findings will help medical cases where these enzymes do not work properly. “Diseases can occur when these enzymes are overactive or not active enough, such as cancer, rheumatoid arthritis and diabetes,” noted Dr. Zhang. “So by understanding how they work, we have a chance to develop chemical molecules to restore their function.”
According to Dr. Zhang, this complicated chemical process that occurs in nature can now be copied by synthetic biologists to engineer a whole new class of medicines, opening new avenues for drug development.