Data-rich process development of immobilized biocatalysts in flow,Reaction Chemistry & Engineering

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Data-rich process development of immobilized biocatalysts in flow
Reaction Chemistry & Engineering ( IF 3.4 ) Pub Date : 2022-01-07 , DOI: 10.1039/d1re00298h
Jacob H. Forstater ₁ , Shane T. Grosser ₁

Affiliation

Immobilization has been widely applied to improve the productivity and lifetime of select enzyme classes used in commodity chemical synthesis. Advances in enzyme engineering capabilities and high throughput experimentation have dramatically increased the use of novel enzyme classes and their applications to pharmaceutical synthesis, where immobilization is used to increase enzyme loading and stability and improve protein-product isolation. Conventional approaches to immobilization development are time and resource-intensive and cannot meet pharmaceutical development's demanding timelines. We developed a data-rich methodology that uses a medium pressure chromatography system to automate the screening and development of affinity-based enzyme immobilizations. We integrated inline PAT to characterize the immobilization process in real-time and facilitate rapid decision making. Most critically, this approach served to significantly reduce the amounts of enzyme and resin required for meaningful process development, transforming immobilization process development and optimization from a manual 6–8 week process to an automated overnight process. This paper demonstrates the development and application of data-rich experimental methods to rapidly identify, develop, and optimize robust, scalable immobilization processes, provide improved fundamental understanding, and describes how this methodology has enabled multiple successful commercial-scale immobilizations.

中文翻译：

流动中固定化生物催化剂的数据丰富的工艺开发

固定化已广泛应用于提高商品化学合成中使用的选定酶类的生产率和寿命。酶工程能力和高通量实验的进步极大地增加了新型酶类的使用及其在药物合成中的应用，其中固定化用于增加酶负载和稳定性并改善蛋白质产品的分离。传统的固定化开发方法是时间和资源密集型的，不能满足药物开发的紧迫时间表。我们开发了一种数据丰富的方法，该方法使用中压色谱系统自动筛选和开发基于亲和力的酶固定化。我们集成了在线 PAT 以实时表征固定过程并促进快速决策。最关键的是，这种方法显着减少了有意义的工艺开发所需的酶和树脂的量，将固定化工艺开发和优化从手动 6-8 周的过程转变为自动化的过夜过程。本文展示了数据丰富的实验方法的开发和应用，以快速识别、开发和优化稳健、可扩展的固定化过程，提供更好的基本理解，并描述了该方法如何实现多个成功的商业规模固定化。这种方法显着减少了有意义的工艺开发所需的酶和树脂量，将固定化工艺开发和优化从手动 6-8 周的过程转变为自动化的过夜过程。本文展示了数据丰富的实验方法的开发和应用，以快速识别、开发和优化稳健、可扩展的固定化过程，提供更好的基本理解，并描述了该方法如何实现多个成功的商业规模固定化。这种方法显着减少了有意义的工艺开发所需的酶和树脂量，将固定化工艺开发和优化从手动 6-8 周的过程转变为自动化的过夜过程。本文展示了数据丰富的实验方法的开发和应用，以快速识别、开发和优化稳健、可扩展的固定化过程，提供更好的基本理解，并描述了该方法如何实现多个成功的商业规模固定化。

更新日期：2022-01-07

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