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

Since its discovery in the 1950s, the Gram-positive soil bacterium Corynebacterium glutamicum has turned into a biotechnological work horse. It is applied worldwide for the production of various products, including 2.5 million t/a glutamate and 1.5 million t/a lysine for the food and feed industry. From early on, the industrial demand for these amino acids strongly stimulated the creation of efficient production strains, including development of progressive techniques that allow strain optimization. With the invention of recombinant DNA technology, a targeted genetic optimization of C. glutamicum became possible. The major challenge toward successful improvement is still the prediction of beneficial optimization targets requiring detailed understanding of the underlying pathways. Hereby, metabolic flux analysis emerged as most valuable technique. Today, powerful state-of-the-art technologies available enable the study of fluxes on various levels, including screening at microliter-scale, routine strain profiling at laboratory scale, or analysis of large-scale production processes. As shown here, flux analysis has provided deep insights into the physiology of Corynebacterium glutamicum, probably the best studied microorganism on the level of metabolic fluxes today.