Development of Databases and Computational Methods for Exploring and Managing Metabolic Complexity

Metabolic engineering has benefited from the application of mathematical methods and the availability of biological databases. Two of the central problems in metabolic engineering have been the expansion of our current knowledge of biochemical reactions and compounds and the identification of targets for manipulating metabolism with the minimum possible impact on cells physiology. We will present and discuss our work in addressing these two problems.

In the first case we will present and discuss the ATLAS of biochemistry, a database of all the biochemically plausible reactions between compounds reported to occur in living organisms. ATLAS uses KEGG as the reference database with 16,000 metabolites and 10,000 reactions and it contains more than 130,000 new reactions. The mining of ATLAS will undoubtedly offer new opportunities for the design of synthetic pathways and metabolic engineering.

In the second case, we will introduce an optimisation framework that (i) uses a kinetic representation of genome-scale metabolic networks, and (ii) identifies enzyme manipulations that can optimize a metabolic function while maintaining metabolite levels and reaction rates within physiological ranges.