Indole generates quiescent and metabolically active Escherichia coli cultures

• Published in: Biotechnology journal 2015-04, Vol.10 (4), p.636-646
• Main Authors: Chen, Chih-Chin, Walia, Rupali, Mukherjee, Krishna J., Mahalik, Subhashree, Summers, David K.
• Format: Article
• Language: English
• Subjects: Bacterial cell factory; Bioreactors - microbiology; Biorefining; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - metabolism; Fermentation; Indole; Indoles - pharmacology; Metabolite production; Quiescent cells; Recombinant Proteins - genetics; Recombinant Proteins - metabolism
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.201400381

An inherent problem with bacterial cell factories used to produce recombinant proteins or metabolites is that resources are channeled into unwanted biomass as well as product. Over several years, attempts have been made to increase efficiency by unlinking biomass and product generation. One example was the quiescent cell (Q‐Cell) expression system that generated non‐growing but metabolically active Escherichia coli by over‐expressing a regulatory RNA (Rcd) in a defined genetic background. Although effective at increasing the efficiency with which resources are converted to product, the technical complexity of the Rcd‐based Q‐Cell system limited its use. We describe here an alternative method for generating Q‐Cells by the direct addition of indole, or related indole derivatives, to the culture medium of an E. coli strain carrying defined mutations in the hns gene. This simple and effective approach is shown to be functional in both shake‐flask and fermenter culture. The cells remain metabolically active and analysis of their performance in the fermenter suggests that they may be particularly suitable for the production of cellular metabolites. In conventional culture, a bacterial cell factory produces unwanted biomass as well as the desired product. Indole treatment produces a quiescent cell factory that generates significantly less biomass while remaining capable of product formation. Quiescent cells offer a significant improvement in the efficiency with which raw materials in the culture medium are converted to product.