Olughu Williams, Nienow Alvin, Hewitt Chris, Rielly Chris
Department of Chemical Engineering Loughborough University Loughborough UK.
Ipsen Biopharma Ltd Wrexham UK.
J Chem Technol Biotechnol. 2020 Mar;95(3):675-685. doi: 10.1002/jctb.6248. Epub 2019 Nov 21.
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 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 ( ), but also the mean frequency at which the bacterial cells entered the PFR ( ) section of the two-compartment reactor.
On implementing this strategy the cadaverine production decreased on average by 26%, 49% and 59% when the 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 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.
This study demonstrated that 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. © 2019 The Authors. published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
生物过程在放大过程中效率和性能的损失是众所周知的，但尚未完全理解。本研究通过使用产尸胺的重组体DM1945 Δact3 Ptuf-ldcC_OPT，在实验室规模的两室反应器[活塞流反应器（PFR）+搅拌釜反应器（STR）]中研究一些在较大规模下出现的发酵梯度（pH、葡萄糖和氧气）的影响，来解决这个问题。这里开发的新的缩小规模策略不仅考虑了PFR中平均细胞停留时间（），还考虑了细菌细胞进入两室反应器PFR部分的平均频率（），研究了增加发酵梯度幅度的影响。
实施该策略后，与对照发酵相比，当分别从1分钟增加到2分钟然后再增加到5分钟时，尸胺产量平均分别下降了26%、49%和59%。在5分钟时二氧化碳生产率最高（是对照的3.1倍），但在生物量生产中未观察到损失。然而，随着发酵梯度幅度的增加，活的但不可培养的细胞数量增加。新的缩小规模方法也显示出比传统方法对发酵性能有更大的影响。
本研究表明，DM1945 Δact3 Ptuf-ldcC_OPT的生理反应是模拟发酵梯度幅度的函数。如这里所观察到的，细菌细胞在异质环境中的适应性最终导致发酵生产力的损失。© 2019作者。由John Wiley & Sons Ltd代表化学工业协会出版。
