Abstract
Microaerobic fermentation has been shown to improve lactose transport and recombinant protein production in Escherichia coli. Mechanistic correlation between lactose and dissolved oxygen has been studied and it has been demonstrated that E. coli can switch its genetic machinery upon fluctuations in dissolved oxygen levels and thereby impact lactose transport, resulting in product formation. Continuous induction of lactose in microaerobic fermentation led to a 3.3-fold improvement in product titre of rLTNF oligomer and a 1.8-fold improvement in product titre of rSymlin oligomer as compared with traditional aerobic fermentation. Transcriptome profiling indicated that ribosome synthesis, lactose transport and amino acid synthesis genes were upregulated during microaerobic fermentation. Besides, novel lactose transporter setB was examined and it was observed that lactose uptake rate was 1.4-fold higher in microaerobic fermentation. The results indicate that microaerobic fermentation can offer a superior alternative for industrial production of recombinant therapeutics, industrial enzymes and metabolites in E. coli.
Key points
• Microaerobic fermentation results in significantly improved protein production
• Lactose transport, ribosome synthesis and amino acid synthesis are enhanced
• Product titre improves by 1.8–3.3-fold
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Acknowledgements
The authors would like to acknowledge Prof. Claire Komives, San Jose State University, USA, for gifting us the (rLTNF) clone.
Funding
This work was financially supported by Department of Biotechnology, Ministry of Science and Technology, under schemes of Centre of Excellence for Biopharmaceutical Technology (BT/COE/34/SP15097/2015) and Indo-US Joint Proposals in the area of low-cost medical devices (BT/PR17497/MED/15/146/2016).
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KAP, ASC and ASR conceived and designed research. KAP and ASC conducted experiments. ASC and JAG contributed to transcriptomic data analysis. KAP, ASC and JAG wrote the first draft. ASR was responsible for project supervision, acquiring funding and creating the final version of the manuscript. All authors read and approved the manuscript.
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Pandi, K., Chauhan, A.S., Gupta, J.A. et al. Microaerobic fermentation alters lactose metabolism in Escherichia coli. Appl Microbiol Biotechnol 104, 5773–5785 (2020). https://doi.org/10.1007/s00253-020-10652-6
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DOI: https://doi.org/10.1007/s00253-020-10652-6