The biotech industry should change production methods
By Mette Haagen Marcussen
Cell factory production can be optimized significantly if the biotech industry move away from production in pure cell cultures and instead use genetic engineering to mimic the microbes’ naturally diverse living conditions in cell factory production. This is the strong suggestion from the researchers behind a new study just published in the prestigious journal Current Biology.
The biotech industry uses living organisms, such as fungi, bacteria and microbes to produce a wide range of products including foods such as cheese, wine and bread, medicine like penicillin, insulin for diabetes patients, and a number of other products used in everyday life, for example ethanol for fuel, laundry powder enzymes, and biodegradable plastic materials.
The Danish biotech industry arose in the 1800s, when J.C. Jacobsen created the Carlsberg Laboratory for the development of pure yeast cultures for beer brewing.
Pure culture is a cultivation method in which a variety of a plant species or culture of bacteria or yeast is cultivated without mixing it with other organisms. The advantage is that it is easier to control production, when you have only one organism.
Since then, the biotech industry has been steadily growing, and it represents an ever-increasing proportion of Danish industrial production. Common to all companies is that they use pure cultures in production.
Diversity gives advanced survival strategies – also in cell factories
As opposed to the pure factory conditions, microbes in nature live in highly diverse communities, where they collaborate with each other for a wide range of tasks. They share the tasks for, for example, for secretion of antibiotics for protection against enemies or for secretion of enzymes to obtain food, and some microorganisms develop into specialists in a particular area to perform the specific task.
When these tasks are divided within the population (one member commits to one task, while other performs a different job), it is called division of labor. The division of labor gives the microorganisms an advanced survival strategy, which for instance enables them to explore new territories, or form fruiting bodies, which ensure a high spread of microorganism spores.
New research from the Technical University of Denmark shows that these advanced survival strategies can be utilized for better cell factory production. By moving away from the traditional pure cell cultures and embarking on a new production method of genetically engineered mixed microbial consortia, cell factory production can be optimized significantly.
Two ways to become a microbial specialist
When the microorganisms are to develop into specialists, they can do it in two ways: either phenotypically, where they retain all of their original genetic abilities, but only use the ones required to perform the task. That way they retain the potential to perform other tasks. The second option is genetic differentiation, in which they completely lose the ability to perform tasks other than those required for them to be specialists.
These two mechanisms are commonly known, but the advantages and disadvantages of the two strategies, as well as which one is most beneficial to the individual or to the whole population has remained unknown.
Genetic specialists do the job better
In the study, researchers combined experimental and computational methods to investigate the potential benefits of division of labor during the development of biofilm using the soil dwelling bacteria Bacillus subtilis. By genomic engineering, they designed two specialists, one that produced polysaccharides (carbohydrates) and one that makes protein fibers, both of which are fundamental in the formation of biofilm.
The results of the experiment were confirmed by computer simulation and clearly showed that genotypic division of labor is more effective than when based on phenotypic differentiation.
At the same time, the study shows that it is possible to reproduce the findings during plant colonization by the bacterium, which is an important factor for plant biocontrol and therefore in green biotechnology.
Professor Ákos T Kovács, who is behind the study says
“This study is a very good example of why the biotech industry needs university researchers to do the basic research. We are the first to show that genetic division of labor increase productivity of these microbes. Our findings can have a very positive impact on the Danish biotech industry that aims to continuously improve microbial cell factory-based processes. The next steps are to test division of labor under industrially relevant conditions.”
The biotech company Novozymes, which produces enzymes in cell factories made of bacteria, constantly seeks to optimize production, and Novozymes Senior Manager Michael Dolberg Rasmussen says to “Ingeniøren”, that
“We have great interest in this type of basic research, and therefore among others we have close ties to DTU. ”
source: Technical University of Denmark