A Model-driven Approach towards Rational Microbial Bioprocess Optimization.,Biotechnology and Bioengineering

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A Model-driven Approach towards Rational Microbial Bioprocess Optimization.
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-09-18 , DOI: 10.1002/bit.27571
Jing Wui Yeoh _{1,

2} , Sudhaghar S/O Jayaraman _{1,

2} , Sean Guo-Dong Tan ₁ , Premkumar Jayaraman _{1,

2} , Maciej B Holowko ₂ , Jingyun Zhang _{1,

2} , Chang-Wei Kang ₃ , Hwa Liang Leo ₁ , Chueh Loo Poh _{1,

2}

Affiliation

Due to sustainability concerns, bio‐based production capitalizing on microbes as cell factories is in demand to synthesize valuable products. Nevertheless, the nonhomogenous variations of the extracellular environment in bioprocesses often challenge the biomass growth and the bioproduction yield. To enable a more rational bioprocess optimization, we have established a model‐driven approach that systematically integrates experiments with modeling, executed from flask to bioreactor scale, and using ferulic acid to vanillin bioconversion as a case study. The impacts of mass transfer and aeration on the biomass growth and bioproduction performances were examined using minimal small‐scale experiments. An integrated model coupling the cell factory kinetics with the three‐dimensional computational hydrodynamics of bioreactor was developed to better capture the spatiotemporal distributions of bioproduction. Full‐factorial predictions were then performed to identify the desired operating conditions. A bioconversion yield of 94% was achieved, which is one of the highest for recombinant Escherichia coli using ferulic acid as the precursor.

中文翻译：

一种模型驱动的合理微生物生物过程优化方法。

由于可持续性问题，需要利用微生物作为细胞工厂的生物基生产来合成有价值的产品。然而，生物过程中细胞外环境的非均质变化常常挑战生物质生长和生物产量。为了实现更合理的生物过程优化，我们建立了一种模型驱动的方法，该方法系统地将实验与建模相结合，从烧瓶到生物反应器规模执行，并以阿魏酸到香草醛的生物转化为案例研究。使用最小的小规模实验研究了传质和曝气对生物质生长和生物生产性能的影响。开发了一种将细胞工厂动力学与生物反应器的三维计算流体动力学耦合的集成模型，以更好地捕捉生物生产的时空分布。然后进行全因子预测以确定所需的操作条件。实现了 94% 的生物转化率，这是重组体中最高的生物转化率之一以阿魏酸为前体的大肠杆菌。

更新日期：2020-09-18

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