Although much of bioprocessing relies on mammalian cells, like Chinese hamster ovary (CHO) cells, to express proteins, many academic and industrial groups use microbial systems. In central North Carolina, for example, contract development and manufacturing organization (CDMO) KBI Biopharma can work with mammalian and microbial expression systems.

“One of KBI Biopharma’s most innovative bioprocessing capabilities lies in its development of the PUREcoli cell line, which represents a significant advancement in microbial manufacturing, particularly in the realm of recombinant-protein expression,” says CEO J.D. Mowery, who adds that the key to this cell line comes from extensive genetic engineering.

“Common E. coli expression strains typically undergo limited genetic alterations to enhance protein expression,” he explains. In the PUREcoli cell line, “approximately 1,000 genes have been altered, and around one million base pairs of DNA have been removed to create a streamlined and optimized genotype.”

Streamlining the genome of E. coli cells

In streamlining the genome of these E. coli cells, KBI eliminated unnecessary genes and reduced translational and post-translational modifications. As a result, says Mowery, “It exhibits nearly 50% faster growth rates in fully defined media and achieves approximately double the cell density compared to common E. coli strains.”

He notes that this cell line even works in the expression of troublesome proteins, which has been a challenge with E. coli-based methods. As scientists from the University of Birmingham and Cobra Biologics, both in the U.K., wrote about using E. coli: “Optimization of recombinant protein production remains problematic as many proteins are difficult to make, and process conditions must be optimized for each individual protein.”

Instead of working to improve E. coli, some scientists switch to different microbes. As recently reported in GEN, for example: “Cornell University scientists have created an engineered version of the bacterium Vibrio natriegens, which they say will offer researchers a low-cost and scalable platform for carrying out synthetic biological experiments.”

Although bioprocessing relies on a range of upstream and downstream steps, the cell line remains fundamental to an efficient and effective process. Consequently, bioprocessors and academic scientists will keep looking for new cell lines and tinkering with the genetics of model organisms like E. coli.

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