SynMet - A synthetic Biology Approach for Engineering of Bacterial Methylotrophy

• Applicant: Professor Dr. Volker Wendisch
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 165336941

One-carbon (C1) compounds such as methane and methanol are attractive, non-food and low-cost carbon and energy sources for microbial bioprocesses, which can be utilized by specialized groups of microorganisms; the methylotrophs. Research efforts with different model strains revealed that methylotrophy consists of a set of discrete functional modules that are ultimately linked to central metabolism. In the different phylogenetic groups of known methylotrophic bacteria, which include Proteobacteria and Gram-positive bacteria, alternative non-orthologous modules exist for C1 conversion. Those ensure oxidation of the reduced C1 source to CO2 for energy generation, and C1 assimilation with or without netto CO2 fixation for biomass formation. Formaldehyde is a key intermediate in bacterial C1 conversion; in consequence, the metabolism of this toxic compound must be very efficient and tightly regulated in order to avoid intracellular accumulation leading to cell death. By integrating genomic and experimental knowledge from different methylotrophic model organisms, e.g. Bacillus methanolicus and Methylobacterium extorquens, we will define - by means of in silico modelling - ideal combinations and minimal sets of modules, and design strategies for their synthetic assembly, transfer, and coordinated expression in biotechnologically important bacterial hosts. It is anticipated that this approach will include generation of hybrid pathways involving the concerted action of heterologous and the hosts’ natural genes. Physiological characterization and omics-approaches including fluxomics will be used to analyse and evaluate the genetically engineered cells with respect to the acquired methylotrophic properties. For further improvement this approach will be repeated iteratively to integrate and/or delete specific genes and operons. The generated knowledge will contribute to an increased understanding of bacterial methylotrophy and will facilitate transfer of methylotrophy to biotechnologically relevant bacteria as a new modular platform for methanol-based production of bulk chemicals.

• DFG Programme: Research Grants