Project Title: Cobalamin biosynthetic enzymes: Explored using structural biology and exploited using synthetic biology
Summary: Cobalamin (vitamin B12) is the most complex molecule found in nature. A remarkable observation in the biosynthesis has shown that several of the enzymes bind their products tightly and therefore have been seen trapped in the determined structures. The trapped enzyme-product complex is the the substrate for the subsequent enzyme in the pathway. The process by which the next enzyme interacts with the enzyme-product complex is intriguing and suggests some form of higher level organisation and these important interactions have yet to be revealed, understaood and exploited in synthetic biology. This work will not only build on our understanding of the fascinating biochemical pathway but may also facilitate the development of novel cobalamin molecules using synthetic biology combined with chemical intervention.