Researchers at the Universidad del Valle (Univalle) are using simulations to predict the conditions under which microbes will increase their production of an ingredient crucial to maintaining the effectiveness of antibiotics.
For decades, the pharmaceutical industry has used the bacterium Streptomyces clavuligerus to produce clavulanic acid, which is already a key ingredient in helping antibiotics such as amoxicillin to be effective in the treatment of diseases resistant to conventional antibiotics.
Colombia has a very high rate of antibiotic use in medical and agricultural uses and a cheaper and faster source of clavulanic acid is essential, among other measures, to improve access to adequate medical treatment in cases of infections that cannot be controlled with generic antibiotics.
“Under conditions of nutritional and environmental stress, the bacteria Streptomyces clavuligerus produce Clavulanic acid —we're looking for the perfect balance to produce the maximum amount of this compound," Professor David Gómez-Ríos said.
“Under conditions of nutritional and environmental stress, the bacteria Streptomyces clavuligerus produce Clavulanic acid —we're looking for the perfect balance to produce the maximum amount of this compound," Professor David Gómez-Ríos said.
Gomez is a faculty member of Univalle's School of Chemical Engineering and is the first author of the paper called “Tuning of fed-batch cultivation of Streptomyces clavuligerus for enhanced Clavulanic Acid production based on genome-scale dynamic modeling,” published in the journal Biochemical Engineering Journal in July 2022.
In the study, the researchers used computational simulations to determine how bacteria can grow in different conditions to decrease the number of tests needed en vivo, that is, with bacteria in the real world.
Image: Streptomyces clavuligerus bacteria from experimental cultures of Professor Gomez's project work. Credit: David Andrés Gómez Ríos.
La Investigación
"Clavulanic acid is relatively expensive compared to generic antibiotics," Profesor Goméz explained, adding that 10 capsules of amoxicillin cost 6000 Colombian Pesos ($1.35 USD) while the same amount of the formulation amoxicillin clavulanate used in the treatment of resistant infections costs at least 48000 pesos ($10.80 USD), that is, 8 times more expensive.
The researchers are looking for a way to lower this cost through a more efficient process within the bioreactors used to grow these bacteria.
Tools known as dynamic metabolic flux analysis and genome-scale metabolic modeling were combined to identify computational strategies to more than double clavulanic acid productivity under conditions that were experimentally verified in pilot-scale bioreactors.
Professor Silvia Ochoa, a faculty memeber at the Department of Chemical Engineering of the Universidad de Antioquia (UdeA) and a co-author of the scientific publication said that the use of these computational tools, although they do not replace experimental work in the laboratory, do allow a better use of resources (in terms of time, money and reduction of environmental impact) to direct experimental developments.
"They constitute an important step in the research towards the development of an antibiotic production industry that can be established in Colombia," Professor Ochoa said.
Read more from Univalle’s School of Chemical Engineering: Univalle Researcher seeks to catalyze chemical reactions... and development for his Indigenous community.
Professor David Gómez-Ríos, a lecturer at Univalle's School of Chemical Engineering Credit: Andrew James/Univa
National and International Collaborations
Professor Ochoa said that the collaborative work between the School of Chemical Engineering of Univalle and the Department of Chemical Engineering of UdeA is strengthened by the presence of Professor Gómez-Ríos and Professor Howard Ramírez, Director of the Applied Chemical and Biological Processes Research Group (BIOQUIMAP).
"In my particular case, I admire, appreciate and deeply value the friendship that unites us, and that has been and will continue to be the foundation for research on the subject of improving the technical-economic feasibility of bioprocesses, so that we can continue to advance in their consolidation in our country," Professor Ochoa said, "We professors of the chemical engineering department at UdeA feel supremely proud that two of our graduates of the doctoral program in chemical engineering are part of the faculty team at Universidad del Valle."
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