Towards stable cyanobacterial cell factories

Irrespective of where we come from, we all share the global responsibility of ensuring that our societies are sustainable. We have been depleting the world’s resources and filling the atmosphere with abnormal levels of CO2. But CO2 can also be used as a resource - plants and certain microbes have been doing so for billions of years. This is the foundation for the bio-based economy – reducing and eventually replacing the use of fossil fuel. Up to now, the focus in bio-based production has been on producing biofuels using plants to produce sugars, which are then used as substrate in microbial fermentation processes. But there is an alternative way - using cyanobacteria to take up CO2 from the atmosphere and directly converting it into useful products. However, the development of efficient cyanobacterial cell factories is still challenging. One typical technical hurdle is to maintain sustained productivity. This is because traditional genetic engineering strategies for microbial product formation, i.e. through introduction of heterologous pathways encoded by multiple genes with constitutive expression levels, are burdensome for cell growth. Consequently, spontaneous non-producing mutants tend to grow faster, thereby gradually taking over the population and undermining the total productivity of the culture. In general, this technical hurdle is common to any microbial system that was genetically engineered for product formation. Yet, for cyanobacteria little attention had been paid before this project commenced. Therefore, we decided to specifically study the instability of cyanobacterial direct conversion processes, aiming for conceiving novel strategies to prevent this problem.