With the addition of a murine-derived biocatalyst (green), this engineered protein can add a fluoride atom to create macrolide analogs (structure, right). This approach offers a greener, more efficient method for creating new antibiotics. Credit: Martin Grininger and Rajani Arora
Key Points:
- Scientists have devised a method that may help them fight antibiotic-resistant bacterial infections.
- Adding a fluorine atom to the synthesis of erythromycin makes the antibiotic more efficient.
- The behavior of a mouse protein allowed them to figure out how to replicate the fluorine atom safely.
Researchers have developed a novel approach to overcome the challenges presented by antibiotic-resistant infections.
German scientists at Goethe University theorized they could increase the antibiotic’s medicinal properties by adding a fluorine atom to the microorganism that produces it. The team’s research, which appears in Nature Chemistry, has the potential to combat antibiotic-resistant bacteria.
"We had been studying fatty acid synthesis for several years, when we uncovered a mouse protein that might be used for directed biosynthesis of these modified antibiotics,” said Martin Grininger, a biomolecular expert at the university.
With the help of David Sherman, who specializes in microbiology and immunology at the University of Michigan, the team employed protein engineering to replace one element of the system's natural mechanism with a fluorine atom. This additional fluorine atom, which behaves similarly to the mouse protein, was found to improve the finished product's capacity to kill bacteria and work safely in patients.
Erythromycin inhibits bacterial survival by binding to the ribosome. Some bacteria, however, block this binding. This unfortunately makes them antibiotic-resistant. The researchers found that adding a fluorine atom to the synthesis of the antibiotic restores its ability to combat the bacteria.
Synthetically adding the fluorine atom, though, is challenging because dangerous chemicals are usually employed during the process. To combat that, researchers created a new biosynthetic process that sidesteps the use of toxic chemicals. They were able to reprogram the microorganism to replicate the process without the use of those chemicals.
Researchers said fluorinated chemicals are still a few years from the clinic. The process they created, however, shows much promise. They hope it will provide for a more efficient way to produce new antibiotics, antivirals, and anti-cancer drugs.