Process control for enhanced L‐phenylalanine production using different recombinant Escherichia coli strains

Abstract
A novel fed‐batch approach for the production of L‐phenylalanine (L‐Phe) with recombinant E. coli is presented concerning the on‐line control of the key fermentation parameters glucose and tyrosine. Two different production strains possessing either the tyrosine feedback resistant aroFfbr (encoding tyrosine feedback resistant DAHP‐synthase (3‐desoxy‐D‐arabino‐heptusonate‐7‐phosphate)) or the wild‐type aroFwt were used as model systems to elucidate the necessity of finding an individual process optimum for each genotype. With the aid of tyrosine control, wild‐type aroFwt could be used for L‐Phe production achieving higher final L‐Phe titers (34 g/L) than the aroFfbr strain (28 g/L) and providing higher DAHP‐synthase activities. With on‐line glucose control, an optimum glucose concentration of 5 g/L could be identified that allowed a sufficient carbon supply for L‐Phe production while at the same time an overflow metabolism leading to acetate by‐product formation was avoided. The process approach is suitable for other production strains not only in lab‐scale but also in pilot‐scale bioreactors. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 746–754, 2002.