Shiloach Joseph, Fass Rephael
Biotechnology Unit, Bldg. 14A Rm. 173, NIDDK, NIH Bethesda, MD 20892-5522, USA.
Biotechnol Adv. 2005 Jul;23(5):345-57. doi: 10.1016/j.biotechadv.2005.04.004.
E. coli is the major bacterial platform for expressing simple heterologous proteins. Growing E. coli to high densities has been the subject of numerous studies since the early 1970s, exploring the limits of bacterial culture density in order to achieve maximum productivity. Research strategies were focused on improving the cultivation techniques, manipulating the bacteria's physiology or both. As a result, batch, fed batch and dialysis fermentation techniques had been developed. These growth strategies, together with optimization of media composition and the application of molecular biology methods, made it possible to grow E. coli to cell densities of up to 190 g/l (dry weight), while avoiding media precipitation and preventing acetate accumulation. Additional research on the effects of heterologous protein biosynthesis on signal transduction, proteolysis and post transcription events in E. coli may improve its productivity.
大肠杆菌是表达简单异源蛋白的主要细菌平台。自20世纪70年代初以来，将大肠杆菌培养至高细胞密度一直是众多研究的主题，旨在探索细菌培养密度的极限以实现最大生产力。研究策略集中在改进培养技术、调控细菌生理特性或两者兼顾。结果，分批培养、补料分批培养和透析发酵技术得以发展。这些生长策略，连同培养基成分的优化和分子生物学方法的应用，使得将大肠杆菌培养至高达190 g/l（干重）的细胞密度成为可能，同时避免了培养基沉淀并防止了乙酸积累。对大肠杆菌中异源蛋白生物合成对信号转导、蛋白水解和转录后事件影响的进一步研究可能会提高其生产力。
