“Bacterial protein-tyrosine kinases: from initial discovery to biotech and biomedical applications”
Dr. Ivan Mijakovic, Professor of Systems Microbiology, Chalmers University of Technology, Sweden
Wednesday, November 25
11:00 a.m. – 12:00 p.m.
Ibn Sina (bldg. 3)
Level 5, Room 5209
In the mid-1990s, the first discoveries were made of bacterial enzymes that autophosphorylate on tyrosine residues. In 2003, we demonstrated for the first time that these enzymes are true kinases and renamed them BY-kinases. They are capable of phosphorylating other cellular proteins and regulating the activity of these protein substrates. In the decade that followed, our group focused on deciphering the physiological role of the BY-kinase PtkA in the model bacterium Bacillus subtilis. It soon became apparent that this kinase phosphorylates a number of protein substrates involved in different cellular processes. More recently, we found out that PtkA kinase can be activated by several distinct protein interactants and is capable of engaging in cross-phosphorylation with other kinases. Evolutionary studies based on genome comparison indicate that BY-kinases exist only in bacteria. They are non-essential (present in about 40% bacterial genomes), and their knockouts lead to pleiotropic phenotypes since they phosphorylate many substrates. Surprisingly, BY-kinase genes accumulate mutations at an increased rate (the non-synonymous substitution rate is significantly higher than other bacterial genes).
One direct consequence of this phenomenon is no detectable co-evolution between kinases and their substrates. Their promiscuity towards substrates thus seems to be “hard-wired,” but why would bacteria maintain such promiscuous regulatory devices? One explanation is the maintenance of BY-kinases as rapidly evolving regulators which can readily adopt new substrates when environmental changes impose selective pressure for the quick evolution of new regulatory modules. Their role is clearly not to act as master regulators dedicated to triggering a single response, but they might rather be employed to contribute to fine-tuning and improving the robustness of various cellular responses. This unique feature makes BY-kinases a potentially useful tool in synthetic biology. While other bacterial kinases are very specific and their signaling pathways insulated, BY-kinase can relatively easily be engineered to adopt new substrates and control new biosynthetic processes. Since they are absent in humans and regulate some key functions in pathogenic bacteria, they are also very promising targets for new antibacterial drugs.
Biography
Ivan Mijakovic is a professor of systems microbiology at the Chalmers University of Technology (Sweden), professor with special responsibilities at the Technical University of Denmark (Denmark) and consulting professor at AgroParisTech (France). He holds a Ph.D. degree in molecular microbiology from the University Paris XI (2003) and a professor habilitation from the University Claude Bernard Lyon (2008). Professor Mijakovic is the Chairman of the Functional Genomics section of the European Federation of Biotechnology, and is a member of the Steering Committee of the European Association for Bacillus research – BACELL. He is one of the pioneers in the field of protein phosphorylation in bacteria. His current research activities comprise signaling and regulation in bacterial physiology, phosphoproteomics, metabolic engineering of bacterial cell factories and development of advanced carbon-based materials for anti-bacterial coating.