MetApp - Systems biology of bacterial methylotrophy for biotechnological products from methanol

Methylotrophy, the ability of microorganisms to use methanol as their sole source of carbon and energy for growth, bears the potential to build value from methanol through production of special, fine, bulk, and fuel chemicals. Methanol is abundant and regarded as an highly attractive non-feed raw material in microbial fermentation. Nature evolved different solutions to harness methanol for the purpose of energy generation and biomass formation. These are reflected best by the two facultative methylotrophic model bacteria Methylobacterium extorquens and Bacillus methanolicus. M. extorquens is a mesophilic Gram-negative that shows flexible carbon source utilization of several one-carbon compounds and possess the serine cycle and ethylmalonyl-CoA pathway for carbon assimilation. It is intensely pigmented due to production of carotenoids. B. methanolicus is a thermophilic Gram-positive which possesses the ribulose monophosphate cycle as key pathway and is the first example of plasmid-dependent methylotrophy. B. methanolicus is a natural overproducer of amino acids, a trait that will be further exploited in the MetApp project.

Our vision is the first application of systems biology to bacterial methylotrophy in order to gain systems-level understanding of evolutionary alternatives of a key metabolic trait.

MetApp encompasses genome-scale modelling, quantitative multi-Omics and high-throughput genetic analysis, tests of orthogonality, data management, and model refinement and abstraction to deduce and experimentally evaluate strategies for methanol-based production of sought-after chemicals.