Research team at Rutgers solves 30 year mystery of how specific enzyme works
In an international collaboration with universities in Poland, Russia and England, Rutgers scientists solved a 30-year mystery of a specific enzyme’s molecular machinery in producing an important antibiotic, which is a key protein used by the immune system to fight off bacteria.
Enzymes are a type of protein, and their primary role is to speed up chemical reactions within the body. Konstantin Severinov, a principal investigator at the Waksman Institute of Microbiology and professor of Molecular Biology and Biochemistry at Rutgers—New Brunswick, studied the enzyme called McbBCD, whose job is to produce an antibody called microcin B, which is specifically deadly against E. coli bacteria.
The research team was able to understand both the production and complicated chemical structure of microcin B by decoding the three-dimensional structure of the enzyme.
This discovery of how the enzyme functions enables scientists to now provide different adaptations of the antibiotic, which will also help to further research on new antibodies in the future.
“Antibiotic resistance is becoming a major problem and, if unchecked, it may throw us back to pre-antibiotic era when people were dying from what is now considered easily curable conditions,” Severinov said.
This discovery is important because it reduces the progression of microbial resistance to antibiotics. He said a way to overcome the problem is to look for new antibiotics, but ones that are different from the ones currently in use because bacteria have already acquired resistance to them.
Severinov, alongside an international team, traced the enzyme’s molecular machinery to understand how the antibody was being produced. After understanding the production, they were able to naturally control the production to create synthetic derivatives, or man-made imitations, of the natural antibody to increase its potency.
Though the discovery is significant, it will most likely not be used in clinical trials. While the understanding of the antibiotic helps in the production of synthetic versions of it, Severinov said there was also the potential possibility that one of the newfound derivatives will not react as anticipated.
As a result, antibacterial molecules such as microcin B are unlikely to make it to market production due to strict regulations and requirements. He said the discovery was still important in uncovering the secret to the production of natural antibiotics.
“But this work must be done for out of an effort of hundreds of labs, every once in a while you get a hit that becomes a real drug. In fact, the story of Rutgers’ Selman Waksman shows this well,” he said.
// Editor's Note: An earlier version of this article incorrectly stated that the enzyme produced an antibody, which has been corrected to the word 'antibiotic'.