Glucose based production of L-methionine with E. coli

The sulfur containing amino acid D/L-methionine (C5H11NO2S) serves a 900.000 tons-per-year feed additives market together with its hydroxyl analog (C5H10O3S). While other amino acids are preferably produced via fermentation, D/L-methionine is still chemically synthesized using acroleine, methyl mercaptane and hydrogen cyanide (HCN). The access to these mostly naphta-derived precursors requires harsh reaction conditions together with high energy inputs. Furthermore substances like HCN are extremely toxic.

On the other side, the production of L-methionine based on glucose via recombinant E. coli prevents disadvantages of the chemical route. Likewise fermentation approaches are very challenging because microbial L-methionine production represents severe metabolic burden for the cells. Cellular energy management as well as the supply of intracellular precursors, reduction equivalents, reduced sulfur and methyl units must be well equilibrated to enable optimum L-methionine access.

This contribution presents systems metabolic engineering results enabling L-methionine production with recombinant E. coli. Basics of L-methionine producers are analyzed studying stoichiometric networks. Additionally, stimulus response experiments are presented allowing model-based identification of metabolic control distribution in L-methionine producing cells. Metabolic engineering targets were identified thereof. Additionally lab-scale fermentation results will be shown elucidating the impact of different process scenarios and sulfur sources. Performance data with product/substrate yields >15% will be presented that underline the feasibility and attractiveness of glucose-based L-methionine production.