Using bacteria to make antibiotics
Another interesting article found via ScienceDaily. Erythromycin is a common antibiotic of the aminoglycoside family; erythromycin was one of the antibiotic choices we had in our Kirby-Bauer assays from Lab 7. Aminoglycosides have bacteriocidal activity, and bind to the larger subunit of bacterial ribosomes. When these compounds bind to ribosomes, they prevent the process of adding amino acids to the growing protein chain during the process of protein synthesis. Currently, erythromycin is primarily made biologically from Saccharopolyspora erythraea, the organism it was originally isolated from. The yield of the antibiotic is poor, and the chemical synthesis of the antibiotic in the laboratory is extremely poor, due to the complex chemical reactions which are involved.
Which brings us to the Science Daily article. Erythromycin is a commonly used antibiotic whose mode of action is markedly different from the β-lactam drugs such as the penicillins. As you can see from the structure above, it has a moderately complicated structure, and it is not produced in very significant amounts by the microorganism which synthesizes it. Furthermore, compounds like these are described as secondary metabolites, which are compounds that are only synthesized by a cell as it enters stationary phase, and the cell is no longer actively growing. Contrast this with a compound like ethanol, produced as the final product of fermentation, so that the longer a culture grows the more ethanol that is produced. Complicating the issue with erythromycin is that biosynthesis requires the action of over a dozen genes. Laboratory chemical synthesis of erythromycin requires 18 steps, and has a yield of about 0.02%. For all of you finance types out there, that’s a pretty poor return on your investment.
The ScienceDaily article describes the major findings of this paper. In brief, scientists at Tufts University have obtained each of the genes responsible for making erythromycin in Saccharopolyspora erythraea, and put those genes into Escherichia coli. This basically will turn E. coli into an erythromycin-producing factory, as it is much easier to grow E. coli in the laboratory than S. erythraea. The process will also make it so that erythromycin is no longer a secondary metabolite, but an end product that will accumulate as a culture grows, in much the same manner as my example of ethanol above.
So, now that we are back from Thanksgiving Break, I declare a bonus opportunity! In the comments, think of any problems with the scenario above, where we are turning E. coli into a factory for the production of erythromycin. I am temporarily setting it up so that all answers must be approved by me before appearing to allow many people to participate for points. Don’t worry, I will release the comments.