Pathways at Work: Metabolic Flux Analysis of the Industrial Cell Factory Corynebacterium glutamicum

Abstract

The Gram-positive soil bacterium Corynebacterium glutamicum is a leading workhorse for the biotechnology industry. Worldwide, engineered strains of the microbe synthetize approximately 6 million tons of the amino acids l-glutamate and l-lysine. In addition to these well-known traditional fermentation products, the portfolio of C. glutamicum has impressively expanded over the past years and meanwhile comprises more than 70 natural and non-natural chemicals, materials, fuels, and health-care products. A major challenge to create superior strains for industrial production has always been and still is the design part, i.e. the identification of the most appropriate targets for genomic optimization into a desired phenotype. Metabolic flux analysis is about deciphering the activity of biochemical reactions and pathways of central carbon metabolism. It probably provides the most understandable insight into the core machinery of a living cell. This core part of metabolism displays the controlling centrepiece for synthetizing all the different molecules of recognized industrial value. One can therefore easily understand that metabolic flux analysis had a huge impact on the industrial career of C. glutamicum since its pioneering days in the 1950s, when the microbe was discovered. Initial approaches used simple isotopic tracer studies and mathematical balancing of fermentation data to assess metabolic fluxes in C. glutamicum for the first time. These techniques have been systematically upgraded into comprehensive technologies and enabled a number of seminal studies of fluxes in C. glutamicum, which provided fascinating and unexpected insights into its lifestyle and laid the foundation for metabolically engineered strains, used today in industry. Today, C. glutamicum probably displays the best studied microorganism on the level of metabolic fluxes. New developments promise an even brighter future.