Microorganisms are natural factories for all sorts of biomolecules, and some of them produce antibiotics that can be very useful in medical practice. This is not a newly discovered fact, but because each microorganism produces its own set of molecules and the rate of production is not very high, it’s been difficult to use this knowledge to manufacture large quantities of needed antibiotics. Now researchers at North Carolina State University have developed a molecular-scale sensor that can detect the production of antibiotics, which would allow the identification of the microorganisms that make them. Once identified, the production of the antibiotic can then be scaled to industrial levels.
The NC State team are focusing on finding and manufacturing new useful macrolides, which often have medically useful characteristics, including working as antibiotics. Erythromycin is a macrolide made by a bacteria, for example.
The researchers repurposed MphR, a protein produced by E. coli bacteria that helps it to evade macrolide antibiotics made by attacking microbes. They selected MphR varieties that were able to activate a fluorescent green protein when macrolides were in their environment. They tested their abilities of detection on erythromycin, showing that many MphR varieties are able to spot it very well.
“Essentially we have co-opted and evolved the MphR sensor system, increasing its sensitivity in recognizing the molecules that we’re interested in,” said Gavin Williams, associate professor of bio-organic chemistry at NC State, in a statement. “We know that we can tailor this biosensor and that it will detect the molecules we’re interested in, which will enable us to screen millions of different strains quickly. This is the first step toward high-throughput engineering of antibiotics, where we create vast libraries of genetically modified strains and variants of microbes in order to find the few strains and variants that produce the desired molecule in the desired yield.”
Study in ACS Synthetic Biology: Development of transcription factor-based designer macrolide biosensors for metabolic engineering and synthetic biology…