GBB seminar serie PhD / Postdoc

Matteo Vajente

Groningen Research Institute of Pharmacy

Protein production in the lithoautotrophic bacterium Cupriavidus necator H16

Cupriavidus necator H16 has attracted significant interest in the synthetic biology community due to its ability to grow using CO2, H2, and O2, making it a potential contributor to the CO2-based bioeconomy. This bacterium can be successfully transformed using both conjugation and electroporation, and several metabolites have been produced under both heterotrophic and autotrophic conditions. However, examples of protein production in this organism remain scarce. In our group, we have engineered C. necator to increase protein yield by integrating the T7 RNA polymerase into the genome under the control of different regulatory elements. We then investigated multiple genetic elements to determine their influence on protein production. Finally, we produced the ene-reductase YqjM using our optimized system and compared the protein yield with the commonly used Escherichia coli BL21(DE3) strain.

Henrik Terholsen

Groningen Research Institute of Pharmacy

Nitroreductase-triggered indazole formation

Indazoles are a privileged group in drug research and are found in many pharmaceutical compounds. Unlike most privileged groups, however, indazoles have not yet been accessed via biocatalytic routes, despite these being frequently discussed in the context of sustainable synthesis. Many traditional chemical methods of preparing indazoles have drawbacks, such as the need for hazardous hydrazine derivatives, noble metal catalysts, and harsh reaction conditions. To address these challenges, we have developed the first enzymatic route for indazoles using nitroreductases (NRs). Furthermore, we have developed an enzymatic cascade reaction involving imine reductases (IREDs) that enables indazoles to be produced from inexpensive, readily available starting materials.