Metabolic Engineering of Bacillus methanolicus: Understanding its C1 Metabolism as a basis for Directed Improvement of L-lysine Production

Metabolic engineering is the purposeful modification of cell metabolism by using recombinant DNA technology. The concept is to use available biochemical and genetic data to describe the metabolite flow in a metabolic network, and then use this to target s pecific genes for manipulations in order to alter the flow of metabolites in a desirable direction. For example can metabolic engineering be used to improve yield and production rate of useful compounds (e.g. amino acids, biopolymers, antibiotics), to abo lish wasteful production of undesired by-products, and to improve cells growth. In addition to its obvious applied value the research within this field contributes to valuable basic knowledge about the dynamics of cellular pathways and networks. Our resea rch on Bacillus methanolicus is largely motivated by its high capability to convert methanol into the commercially important amino acids L-lysine and glutamate at 50oC. Genetic and physiological characterization has indicated several unique features of th is bacterium which opens for metabolic engineering strategies of high originality. Experimental metabolic engineering in B. methanolicus has until now been limited due to the lack of functional recombinant tools, and this bottleneck has recently been elim inated by us. The principal objective with the proposed project is to use metabolic engineering to understand B. methanolicus intermediary C1-metabolism at several levels, from initial methanol assimilation to the L-lysine biosynthetic pathway. And, by co mbining the knowledge generated we shall apply rational approaches to improve both the methylotrophic properties as well as the L-lysine production of B. methanolicus. Norway is a large producer of methanol, and the proposed project is expected to contrib ute to a better utilization of this raw material into the production of natural compounds important for human and animal health. The proposed project is basic science and with a high applied potential.