Team:UCopenhagen/Protein Production System

Critical evaluation of our pure protein production system

We know that our product isn't the only way of purifying proteins. Therefore, we have tried to face the reality and find out how well our system perform compared to other production method. This evaluation is based on our very valuable internal discussions and what we have learned by speaking with experts.

Potential drawbacks

1.Efficiency

Our system probably can't come even close to current methods used in Pharmaceutical Industry, for example using E. coli or yeast pichia pestoris. It is not difficult to imagine huge bioreactors able to grow bacteria in volumes of broth up to few hundred litters at a time. Since we are limited with the surface of the membrane upon which our secretion system is dependent, it is not hard to imagine that in bioreactors where the whole volume is used for production of needed protein have higher yield. Even though we don't have exact numbers yet it is probably safe to assume that efficiency will be probably lower than of the current methods used in Pharmaceutical industry.

2.Size and complexity of the protein

Since proteins in our system are secreted in unfolded state there is a serious limitation in how big/complex the proteins can be. Only proteins that are able to fold on their own are appropriate for our system. It goes without saying that absence of PTM (post translational modifications) is almost a prerequisite.

3. Robustness of the process

Due to presence of highly delicate membrane which is crucial both for the integrity of the system (keeping bacteria from contaminating the injectable protein solution) and for the whole process of production of protein via secretion through it, this can be actually considered as "the weakest link in the chain". More work is required for characterising the properties of the membrane.

4.Presence of living potentially pathogenic bacteria

Since bacterial cells are not lysed (as in traditional protein production methods) the presence of living microorganisms - stepwise so close to the final product - this presents a certain risk, considerably higher than if the cell lysate had to undergo a number of purifications and analysis steps.

However there are also advantages of our system:

1. There is no other way to produce protein in space

Arguably they could produce it the "traditional way" – that is growing bacteria and then lysing it, isolating the protein from the lysate, purifying it etc… but that would be extremely difficult to do in absence of gravity and very hazardous in closed space of space station/spaceship. Also the amounts of water and chemicals for protein purification are prohibitively high for a space mission where water is scarce. The fact that astronauts are living in closed space with artificial circulation of air makes any release of potentially pathogenic bacteria very dangerous.

2.There is no "safer" way to produce protein in space

As mentioned above closed systems for handling bacteria are more desirable than "open" systems.

3.Purification steps are effectively eliminated

Protein is secreted in it pure form across the membrane thus eliminating expensive and labour intensive purifying steps.

4.Less biohazard waste produced

Some biohazard waste will inevitably be produced, but in considerably smaller quantities than via "usual" process of lysis and purification

5.No presence of lipopolysaccharides

Further improvement would be using E.coli strains with disabled lipopolysaccharide production, which could be another safety measure.

6.Produce what you need when you need and in quantities you need

Suppose a special protein for quite rare illnesses is needed. It is hard to expect that we will have a cure for every illness in the medicine kit onboard the spaceship. And even the medicines that we took from earth, what happens when we run out of them?

Conclusion

It is up to reader to make the judgment whether the system seems promising in the context of space exploration or not. Considering that not much research has been done about medicine production in space, our system could very well address several of the serious issues connected with "traditional" protein production in space. However due to extraordinary simplicity it could also find its uses on Earth, where the transportability of the system, could be used in desolate areas or underdeveloped regions.