Microbial Biotechnology

Microbial Biotechnology

In microorganisms thousands of chemical reactions can run at the same time. Mankind has used this ability to produce several goods, first in the form of food, as wine and cheese, later also in the form of pharmaceuticals and fine chemicals. Due to current environmental crises like global warming, acidification because of ammonia emissions, deforestation, etc, there is a strong need to reduce the consumption of fossil resources and instead produce bulk chemicals and fuels in a sustainable way. Microbial bioconversion technologies can play a key role in this development. However, bulk chemicals and fuels have low added values, and the current microbial bioconversion technologies cannot yet compete with most existing petrochemical processes. There is one notable exception: the production of bioethanol as fuel by yeasts. Breakthroughs are therefore required to drastically reduce costs of other biotechnological processes.

Mission

To create breakthrough technology for the sustainable and competitive production of (bulk) chemicals and fuels by microorganisms.

Strategy

On our route to this mission, we focus on a number of aspects to develop new biotechnological processes combining our expertise and to enforce a breakthrough.

Expertises

Redox-neutral conversion

The metabolic pathway used for ethanol production is able to transfer all electrons present in sugar to ethanol, and this is the only way to approach the maximum theoretical yield. The metabolic pathways used in other conversions often result in a surplus of electrons. Aerobic respiration is used in these cases to transfer the surplus electrons to oxygen, forming water. This results in lower yields. The challenge is hence to find pathways, or combinations of pathways, that are able to produce these other compounds in a redox-neutral way.

Net ATP-production

The conversion of sugars into ethanol has a negative Gibbs-free energy and yeast are able to conserve a part of this energy in the form of ATP. This ATP is used to support growth and maintenance. The production of most other products does not result in net ATP-production and other energy-conserving processes like aerobic respiration are necessary. Finding alternative ways of energy conservation is therefore evidently important.

Reduce oxygen utilization

Oxygen utilization is a slow process due to the low solubility of oxygen in water. Both redox-neutral pathways and net ATP-production during product formation decrease or nullify oxygen requirements of the process. This results in substantially higher productivities.

Growth uncoupled production

Many compounds are only formed when microorganisms are growing. This means that a significant portion of the substrate is used for growth and is not available for product formation. Yeast is able to produce ethanol when it is not growing, and this contributes to the high yield. Uncoupling product formation from growth is therefore an important aspect to consider.

Energy management

The energy conserved from substrate conversion is not only used for product formation, but also consumed by other cellular processes, for example protein turn-over. Understanding what processes these are and their contribution in energy consumption but also to survival and productivity, will lead to targets to improve energy management for product formation and productivity.

Survival under industrial conditions

The desired products are often toxic to the microorganisms. Many microorganisms are not able to tolerate e.g., 5 g/l of ethanol. Yeast, however, is tolerant to 150 g/l of ethanol and is therefore able to maintain a high productivity over a long period. Also, other factors of the industrial environment may affect the survival and productivity of microorganisms, such as low pH and fluctuations in nutrient availability. Increasing resistance against such stresses, incl. product tolerance, is therefore necessary to improve microbial processes.

Phase separation

Product separation can contribute up to 40 % of the total costs of the microbial production of chemicals. Ethanol is separated by distillation, a relatively cheap phase separation technology. Other phase separations should be considered to reduce separation costs.

Techniques

In our theme group we combine different techniques and analyses in our research. These include amongst others; bioreactor cultivations, enzyme assays, fluorescence-based technologies, metabolic modelling, (CRISPR-Cas based) genetic modifications, evolutionary engineering and other analytical techniques.

Projects

On the right side of this page, you can find our current PhD and Postdoc projects in which these issues are addressed. You can contact us, or the PhD-candidates and post docs directly for more information.