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From scratch to value: engineering Escherichia coli wild type cells to the production of l-phenylalanine and other fine chemicals derived from chorismate

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Abstract

Recombinant strains of Escherichia coli K-12 for the production of the three aromatic amino acids (l-phenylalanine, l-tryptophan, l-tyrosine) have been constructed. The largest demand is for l-phenylalanine (l-Phe), as it can be used as a building block for the low-calorie sweetener, aspartame. Besides l-Phe, an increasing number of shikimic acid pathway intermediates can be produced from appropriate E. coli mutants with blocks in this pathway. The last common intermediate, chorismate, in E. coli not only serves for production of aromatic amino acids but can also be used for high-titer production of non-aromatic compounds, e.g., cyclohexadiene-transdiols. In an approach to diversity-oriented metabolic engineering (metabolic grafting), platform strains with increased flux through the general aromatic pathway were created by suitable gene deletions, additions, or rearrangements. Examples for rational strain constructions for l-phenylalanine and chorismate derivatives are given with emphasis on genetic engineering. As a result, l-phenylalanine producers are available, which were derived through several defined steps from E. coli K-12 wild type. These mutant strains showed l-phenylalanine titers of up to 38 g/l of l-phenylalanine (and up to 45.5 g/l using in situ product recovery). Likewise, two cyclohexadiene-transdiols could be recovered.

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Acknowledgments

The author thanks Prof. Hermann Sahm, Institute of Biotechnology (IBT), Research Center Jülich, Germany, for support of his work at Jülich (1987–2003). I also want to thank Prof. Christian Wandrey who contributed to build up stimulating and fruitful collaborations of microbial geneticists, metabolic, and bioprocess engineers at this unique location. The major part of the work at Jülich was performed in research projects FAME and CHORUS in a close collaboration of Research Center Jülich and DSM Biotech GmbH Jülich and was funded by the German Federal Ministry of Education and Research (grant numbers 0311644 and 0312688). My special thanks are to Ursula Degner and Regine Halbach for expert technical assistance. I want to express my sincere gratitude to my colleagues Marcel Wubbolts, Roel Bovenberg, Leon Raeven (all of DSM Biotech), and to Johannes Bongaerts (both IBT and DSM Biotech), Marco Oldiges, Ralf Takors, and Michael Müller (to name only a few of many co-workers).

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  1. Institute of Microbiology, Universität Stuttgart, Allmandring 31, 70569, Stuttgart, Germany

    Georg A. Sprenger

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Sprenger, G.A. From scratch to value: engineering Escherichia coli wild type cells to the production of l-phenylalanine and other fine chemicals derived from chorismate. Appl Microbiol Biotechnol 75, 739–749 (2007). https://doi.org/10.1007/s00253-007-0931-y

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