Engineering cell physiology to enhance recombinant protein production in Escherichia coli.pdf

MINI-REVIEW Engineering cell physiology to enhance recombinant protein production in Escherichia coli C. Perry Chou Received: 27 February 2007 /Revised: 8 May 2007 /Accepted: 21 May 2007 # Springer-Verlag 2007 Abstract The advent of recombinant DNA technology has revolutionized the strategies for protein production. Due to the well-characterized genome and a variety of mature tools available for genetic manipulation, Escherichia coli is still the most common workhorse for recombinant protein production. However, the culture for industrial applications often presents E. coli cells with a growth condition that is significantly different from their natural inhabiting envi- ronment in the gastrointestinal tract, resulting in deteriora- tion in cell physiology and limitation in cell’s productivity. It has been recognized that innovative design of genetically engineered strains can highly increase the bioprocess yield with minimum investment on the capital and operating costs. Nevertheless, most of these genetic manipulations, by which traits are implanted into the workhorse through recombinant DNA technology, for enhancing recombinant protein productivity often translate into the challenges that deteriorate cell physiology or even jeopardize cell survival. An in-depth understanding of these challenges and their corresponding cellular response at the molecular level becomes crucial for developing superior strains that are more physiologically adaptive to the production environ- ment to improve culture productivity. With the accumulated knowledge in cell physiology, whose importance to gene overexpression was to some extent undervalued previously, this review is intended to focus on the recent biotechno- logical advancement in engineering cell physiology to enhance recombinant protein production in E. coli. Keywords Cell physiology . Escherichia coli . Gene expression . Heat shock . Physiological stress . Recombinant protein . Stress response Introduction With many attract