Cascade enzymatic synthesis of L-homoserine – mathematical modelling as a tool for process optimisation and design,Reaction Chemistry & Engineering

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Cascade enzymatic synthesis of L-homoserine – mathematical modelling as a tool for process optimisation and design
Reaction Chemistry & Engineering ( IF 3.4 ) Pub Date : 2020-01-27 , DOI: 10.1039/c9re00453j
M. Česnik _{1,

2,

3,

4} , M. Sudar _{1,

2,

3,

4} , K. Hernández _{5,

6,

7,

8,

9} , S. Charnock _{10,

11} , Đ. Vasić-Rački _{1,

2,

3,

4} , P. Clapés _{5,

6,

7,

8,

9} , Z. Findrik Blažević _{1,

2,

3,

4}

Affiliation

L-Homoserine is an important compound and a building block in the chemical and pharmaceutical industry. The one-pot cascade synthesis of L-homoserine with substrate recycling catalysed by an aldolase and a transaminase was investigated in detail, with special interest in the reaction's kinetics and process development. Complex relationships between the process variables were discovered and kinetic and reactor models were developed. In addition, new chemical insights were developed through this model-driven process development, and for the first time, a kinetic model was proposed to describe YfaU-catalysed reactions. The modelling was crucial for a better understanding of the reaction system, as well as for process optimisation. Finding a suitable strategy for process improvement by manipulating the reaction conditions, as well as developing a process design, was imperative to obtain the process metrics necessary for scale-up. Using the optimized reaction conditions in the fed-batch reactor with a continuous formaldehyde supply, and with subsequent addition of pyruvate and L-alanine, 80.1 g L⁻¹L-homoserine was obtained with a volume productivity of 3.2 g L⁻¹ h⁻¹ after 25 h. These results present a 100% increase in product concentration and an approximately 18% increase in volume productivity in comparison with previously published work. This work shows the benefit of the synergistic approach of bio(chemical) knowledge and process model development working hand-in-hand which is crucial for greater breakthroughs of biocatalysis in the chemical industry.

中文翻译：

L-高丝氨酸的级联酶促合成-作为过程优化和设计工具的数学建模

L-高丝氨酸是化学和制药工业中的重要化合物和组成部分。L的一锅级联反应用醛缩酶和转氨酶催化底物回收的高丝氨酸进行了详细研究，特别是对反应动力学和工艺开发的关注。发现了过程变量之间的复杂关系，并建立了动力学和反应器模型。此外，通过这种模型驱动的过程开发，获得了新的化学见解，并且首次提出了动力学模型来描述YfaU催化的反应。建模对于更好地了解反应系统以及优化过程至关重要。必须通过控制反应条件以及开发工艺设计来找到合适的工艺改进策略，以获取扩大规模所需的工艺指标。大号丙氨酸80.1克L- ^-1大号用3.2克L-体积生产力获得高丝氨酸^-1 ħ ^-1 25小时后。与以前发表的工作相比，这些结果表明产品浓度提高了100％，体积生产率提高了约18％。这项工作显示了生物（化学）知识和过程模型开发协同工作的协同方法的好处，这对于化学工业中生物催化的更大突破至关重要。

更新日期：2020-01-27

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