Rational Medium Optimization Based On Comparative Metabolic Profiling Analysis To Improve Fumaric Acid Production

Fumaric acid is widely used in the fields of materials, medicine, dope and resin,food and feed additives and has been identified one of the top twelve building block chemicals in the 21 st century by the US Department of Energy. Nowadays,microbial fermentation route displaces chemical synthesis routes to carry out large-scale industrial production of fumaric acid is a natural choice. Rhizopus. oryzae was one of the good-producing strains for fumaric acid production, but the species are limited by genetic engineering due to low efficiency of recombinant DNA and site-specific recombination. So it is not easy to effectively improve the fumaric acid production by operation of the genes.To rationally guide fumaric acid production improvement, metabolic profiling approach was performed to analyze metabolite changes of Rhizopus oryzae FM19 under different fermentation conditions. A correlation between the metabolic profiling and fumaric acid production was revealed by principal component analysis as well as partial least squares. Citric acid, oxaloacetic acid, 2-oxoglutarate, lactic acid, proline, alanine, valine, leucine were identified to be mainly responsible for the metabolism difference, which were involved in the Embden–Meyerhof–Parnas, tricarboxylic acid cycle, amino acid metabolism and fatty acid metabolism.Through the further analysis of metabolites changes together with the above pathways, exogenous addition strategies were developed, which resulted in 14% increase of fumaric acid(up to 56.5 g/L) and less by-products. These results demonstrated that metabolic profiling analysis could be successfully applied to the rational guidance of medium optimization and the productivity improvement of value-added compounds.