01 June 2015

"Microboreactors" for the synthesis of antibiotics

Geneticists have taught E. coli to produce an antibiotic for pneumonia

RIA News

Scientists have created several new strains of E. coli, which converts sugars and other nutrients into molecules of three new super–effective varieties of erythromycin, an antibiotic that is used to fight pneumonia and diphtheria, according to an article published in the journal Science Advances (Zhang et al., Tailoring pathway modularity in the biosynthesis of erythromycin analogues heterologically engineered in E. coli).

Since the discovery of penicillin in the late 20s of the last century, doctors and biologists have been in a constant "arms race" with microbes. The potential of natural antibiotics is almost exhausted, and scientists have to search more and more actively for new sources of bactericidal substances or try to synthesize them in the laboratory, for which millions of dollars are already being spent today.

For this reason, bioengineers have been trying for a long time to shift this task to bacteria, teaching them to synthesize antibiotic molecules and make small arbitrary changes to them, thereby masking them from the protective systems of pathogens.

Blaine Pfeifer from the University of Buffalo (USA) and his colleagues have been working for more than a decade to create such a type of ordinary E. coli (Escherichia coli), which could simultaneously synthesize several varieties of erythromycin, a popular antibiotic today, and not die from it.

The problem is that many of the genes and cellular mechanisms that the bacterium Saccharopolyspora erythraea uses to assemble erythromycin molecules are missing inside the E. coli. For almost 11 years, Pfeiffer and his colleagues have been working on transferring parts of this biomolecular "conveyor" into the DNA of E. coli, and adapting it to work in a new organism.

Having made sure of the stability of this chain of genes and enzymes, the scientists went further and tried to modify it so that the structure of the erythromycin produced by the bacterium could be freely changed by adding new carbohydrate "tails" to the "framework" of the antibiotic. Along the way, scientists have replaced several links of this "pipeline", making its work 2-3 times more efficient than in Saccharopolyspora erythraea.

Using this set of genes, the scientists grew several new strains of E. coli, each of which produced its own version of erythromycin. As shown by tests on cultures of hay Bacillus (Bacillus subtilis), which were invulnerable to the action of the normal version of this antibiotic, three of the nine new varieties of erythromycin were able to overcome their defenses.

"We have not only created new analogues of erythromycin, but also created a platform for the development of drugs based on it. This opens the way for additional experiments in the future, and the creation of new versions of the antibiotic unknown to bacteria," concludes Pfeifer (in a press release, University at Buffalo Engineers turn E. coli into tiny factories for producing new forms of popular antibiotic – VM).

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