With the increased demand for bio-based products and the rapid development of biomanufacturing technologies, biocatalytic reactions including microorganisms and enzyme based, have become promising approaches. Prior to the scale-up of production process, environmental and economic feasibility analysis are essential for the development of a sustainable and intelligent bioeconomy in the context of industry 4.0. To achieve these goals, process simulation supports system optimization, improves energy and resource utilization efficiencies, and supports digital bioprocessing. However, due to the insufficient understanding of cellular metabolism and interaction mechanisms, there is still a lack of rational and transparent simulation tools to efficiently simulate, control, and optimize microbial/enzymatic reaction processes. Therefore, there is an urgent need to develop frameworks that integrate kinetic modeling, process simulation, and sustainability analysis for bioreaction simulations and their optimization. This review summarizes and compares the advantages and disadvantages of different process simulation software and models in simulating biocatalytic processes, identifies the limitations of traditional reaction kinetics models, and proposes the requirement of simulations close to real reactions. In addition, we explore the current state of kinetic modeling at the microscopic scale and how process simulation can be linked to kinetic models of cellular metabolism and computational fluid dynamics modeling. Finally, this review discusses the requirement of sensitivity analysis and how machine learning can assist with optimization of simulations to improve energy efficiency and product yields from techno-economic and life cycle assessment perspectives.

中文翻译：

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放大生物催化系统的工艺模拟和评估：进展、挑战和未来展望


随着对生物基产品需求的增加和生物制造技术的快速发展，包括微生物和酶基在内的生物催化反应已成为有前途的方法。在扩大生产过程之前，环境和经济可行性分析对于在工业 4.0 背景下发展可持续和智能的生物经济至关重要。为了实现这些目标，过程仿真支持系统优化，提高能源和资源利用效率，并支持数字生物工艺。然而，由于对细胞代谢和相互作用机制的了解不足，仍然缺乏合理和透明的模拟工具来有效地模拟、控制和优化微生物/酶反应过程。因此，迫切需要开发集成动力学建模、过程模拟和可持续性分析的框架，用于生物反应模拟及其优化。本文总结和比较了不同过程模拟软件和模型在模拟生物催化过程中的优缺点，确定了传统反应动力学模型的局限性，并提出了接近真实反应的模拟要求。此外，我们还探讨了微观尺度动力学建模的现状，以及过程模拟如何与细胞代谢动力学模型和计算流体动力学建模联系起来。最后，本文从技术经济和生命周期评估的角度讨论了敏感性分析的要求以及机器学习如何协助优化模拟以提高能源效率和产品产量。