Scale-down studies for the scale-up of a recombinant Corynebacterium glutamicum fed-batch fermentation: loss of homogeneity leads to lower levels of cadaverine production

Williams Olughu*, Alvin Nienow, Chris Hewitt, Chris Rielly

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) that occur at the larger scale in a bench-scale two-compartment reactor [plug flow reactor (PFR) + stirred tank reactor (STR)] using the cadaverine-producing recombinant Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The new scale-down strategy developed here studied the effect of increasing the magnitude of fermentation gradients by considering not only the average cell residence time in the PFR (τPFR), but also the mean frequency at which the bacterial cells entered the PFR (fm) section of the two-compartment reactor. RESULTS: On implementing this strategy the cadaverine production decreased on average by 26%, 49% and 59% when the τPFR was increased from 1 to 2 min and then 5 min respectively compared to the control fermentation. The carbon dioxide productivity was highest (3.1-fold that of the control) at a τPFR of 5 min, but no losses were observed in biomass production. However, the population of viable but non-culturable cells increased as the magnitude of fermentation gradients was increased. The new scale-down approach was also shown to have a bigger impact on fermentation performance than the traditional one. CONCLUSION: This study demonstrated that C. glutamicum DM1945 Δact3 Ptuf-ldcC_OPT physiological response was a function of the magnitude of fermentation gradients simulated. The adaptations of a bacterial cell within a heterogeneous environment ultimately result in losses in fermentation productivity as observed here.

Original languageEnglish
JournalJournal of Chemical Technology and Biotechnology
Early online date21 Nov 2019
DOIs
Publication statusE-pub ahead of print - 21 Nov 2019

Bibliographical note

© 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords

  • biochemical engineering
  • bioprocesses
  • biotechnology
  • fermentation
  • industrial biotechnology
  • process development

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