Enhanced expression of soluble antibody fragments by low-temperature and overdosing with a nitrogen source

Se Jun Kim, Gyong Sik Ha, Gyunghwa Lee, Sung In Lim, Chung Min Lee, Yoo Hee Yang, Jae Min Lee, Ju Eun Kim, Jae Hee Lee, Yong Uk Shin, Chan wha Kim, Dong Eok Lee

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Escherichia coli has been a primary host for the prokaryotic production of antibody fragments (Fabs) and has contributed to several successes in the pharmaceutical industry. Nevertheless, the requirement of disulfide bonds often results in low-yield fermentation and a lack of cost-effectiveness. Despite the improved production of functional Fabs by fermentation below 30 °C, the limited cellular growth needs further work. To address these issues, we investigated the effect of nitrogen supply on the cellular growth and the Fab productivity. We used the anti-human VEGF-A Fab as a model that exhibited poor expression at 37 °C regardless of the amount of nitrogen supplied during fermentation. In stark contrast, the expression yield of soluble Fab with a gross nitrogen supply of 6.91 g/L of broth throughout the fermentation at 25 °C was 332 mg/L. Furthermore, and increased nitrogen supply of 10.9 g/L significantly improved the yield of active form by 59.7% and the cellular growth rate by 39.3%. These results indicate that overdosing of a nitrogen source at low temperature is critical to Fab productivity in E. coli.

Original languageEnglish
Pages (from-to)9-15
Number of pages7
JournalEnzyme and Microbial Technology
Publication statusPublished - 2018 Aug


  • Antibody fragment
  • Fed-batch fermentation
  • Low-temperature
  • Nitrogen effect
  • Soluble Fab

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology


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