Scientists produced for the first time a drug that won’t allow animal cruelty and is also very accessible, by modifying common bacteria.
The dietary supplement was designed to address arthritis, and it replaces another food supplement that originated from the cow trachea.
The findings have been published in Nature Communications. The discovery switched the E.coli bacteria from a threat to a ‘blessing’ which produces unlimited chondroitin sulfate in an animal-free environment!
Genetically-modified E.coli can have plenty of medical applications. However, it took a long time to manipulate the bacteria into providing essential medicine elements, such as sulfated glycosaminoglycans that are ‘simplest in this class’.
Mattheos Koffas, lead researcher and a professor of chemical and biological engineering at Rensselaer Polytechnic Institute stated:
“It’s a challenge to engineer E. coli to produce these molecules, and we had to make many changes and balance those changes so that the bacteria will grow well”
He also added:
“But this work shows that it is possible to produce these polysaccharides using E. coli in animal-free fashion, and the procedure can be extended to produce other sulfated glycosaminoglycans.”
How It All Started….
To reach this goal, Koffas had two scientific partnerships: Jonathan Dordick, a fellow chemical and biological engineering professor, and Robert Linhardt, a chemistry and chemical biology professor. The three are members of the Center for Biotechnology and Interdisciplinary Studies.
Linhardt, a pioneer in designing a synthetic variant of heparin, states that the new process of delivering the drug is superior over the old extractive fashion and the chemoenzymatic process.
“If we prepare chondroitin sulfate chemoenzymatically, and we make one gram, and it takes a month to make, and someone calls us and says, ‘Well, now I need 10 grams,’ we’re going to have to spend another month to make 10 grams,” Linhard declared. “Whereas, with the fermentation, you throw the engineered organism in a flask, and you have the material, whether it’s one gram, or 10 grams, or a kilogram. This is the future.”
“The ability to endow a simple bacterium with a biosynthetic pathway only found in animals is critical for synthesis at commercially relevant scales. Just as important is that the complex medicinal product that we produced in E. coli is structurally the same as that used as the dietary supplement.”
Koffas revealed the three stages of bacteria in order to provide chondroitin sulfate: first coupling a gene cluster to obtain an unsulfated polysaccharide precursor molecule,then designing a bacteria that create an ample supply of ‘an energetically expensive sulfur donor molecule’ and the last step was adding a sulfurtransferase enzyme to introduce the sulfur donor molecule to the unsulfated polysaccharide precursor molecule.The stage in which it was added a working sulfotransferase enzyme posed greater difficulty.
“The sulfotransferases are made by much more complex cells,” Koffas said. “When you take them out of a complex eukaryotic cell and put them into E. cold, they’re not functional at all. You basically get nothing. So we had to do quite a bit of protein engineering to make it work.”
The scientists preliminary created an enzyme structure that could make a stable version to work with E.coli using an algorithm that spots the necessary mutations that leads to their goal.
Even the mutated E.coli can generate only a little yield, such as micrograms per liter, the aspect is not an issue in typical lab conditions.
Deepak Vashishth, director of the CBIS, added:
“This work is a milestone in engineering and manufacturing of biologics, and it opens new avenues in several fields such as therapeutics and regenerative medicine that need a substantial supply of specific molecules whose production is lost with aging and diseases.”
“Such advances take birth and thrive in interdisciplinary environments made possible through the unique integration of knowledge and resources available at the Rensselaer CBIS.”
Source: Common bacteria modified to make designer sugar-based drug