More Efficient And Eco-friendly Method To Produce Antibiotics: New Research
An international team of researchers has discovered a method for modifying one type of antibiotic by exploiting tiny organisms that naturally make these molecules. The results, reported in Nature Chemistry on July 25th, might lead to a more efficient synthesis of antibiotics that are effective against drug-resistant bacteria. The Volkswagen Foundation, the LOEWE programme of the state of Hesse, and the National Institutes of Health funded this study.
Experiment Explanation
The researchers began with a microbe that has been genetically modified to generate the antibiotic erythromycin.
Scientists from Germany’s Goethe University’s Institute of Organic Chemistry and Chemical Biology wondered whether the system might be genetically tweaked to build the antibiotic with one more fluorine atom, which may typically boost medicinal qualities.
“We had been studying fatty acid synthesis for several years when we discovered a part of a mouse protein that we thought could be used for directed biosynthesis of these modified antibiotics if added to a biological system that can already make the native compound,” said Martin Grininger, a biomolecular chemistry professor at Goethe University.
The scientists employed protein engineering to substitute one portion of the system’s natural machinery with the functionally comparable mouse gene, in collaboration with David Sherman’s group at the University of Michigan, which specializes in this biological assembly system.
“It’s the equivalent of taking one engine part from a Mercedes and putting it in a Porsche to create a better hybrid engine. You get a Porsche engine that can do new things and is more efficient “Sherman is a member of the University of Michigan Life Sciences Institute and a professor of medicinal chemistry in the College of Pharmacy.
“We can now use protein engineering to create novel molecules with this extremely coveted fluorine atom, which chemists have long struggled to add to macrolide antibiotics.”
This extra fluorine atom is beneficial since it alters not just the finished product’s structure, but also it’s capacity to destroy germs and operate safely in patients.
Erythromycin’s role in this research
Erythromycin functions by attaching to and inhibiting the action of the bacterial ribosome, which is required for bacterial survival. Some bacteria have found strategies to avoid this binding, rendering them resistant to antibiotic therapy. This evolutionary advantage is overcome by adding a fluorine atom to the antibiotic’s structure, restoring the compound’s capacity to kill bacteria.
While scientists have devised ways for synthetically adding fluorine, the procedure is laborious and necessitates the use of harmful chemical reagents. The novel biosynthetic approach developed by Goethe University and the University of Michigan solves these obstacles.
Researcher’s View of this research
“It’s a very exciting finding because it allows us to avoid all of the time-consuming synthetic stages and toxic chemicals,” Sherman said.” Further, we’ve demonstrated that we can reprogram an organism to produce the fluorinated product directly.”
The researchers highlight that the fluorinated chemicals will not be available in the clinic for some years. However, the findings suggest a more efficient road forward for generating novel antibiotics, as well as antivirals and anti-cancer drugs.
“Our strategy has proven successful on a small set of antibiotics,” Grininger said. “But it might eventually be utilised to generate a large range of medications with minimum utilisation of harmful chemicals and by-products.”
Reference Article
Alexander Rittner, Mirko Joppe, Jennifer J. Schmidt, Lara Maria Mayer, Simon Reiners, Elia Heid, Dietmar Herzberg, David H. Sherman, Martin Grininger. Chemoenzymatic synthesis of fluorinated polyketides. Nature Chemistry, 2022; DOI: 10.1038/s41557-022-00996-z
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