Microbial cell factories have been used for the production of valuable chemical compounds using a classical metabolic engineering approach, but this requires much time and cost, and labor‐intensive processes to make cell factories industrially competitive. Systems metabolic engineering is an upgraded version, which understands the cell as a complex system in which networks of genes, transcripts, proteins, and metabolites are connected, facilitating the analysis of potential cell factories. However, efficient cell factory design, which aims for industrial‐scale production, requires a comprehensive system, which goes beyond metabolism and considers industrial production challenges. A review is provided here of the developments and challenges in the application of systems biology for metabolic engineering and in recovery and purification processes for scaling up bio‐based chemical production. Then, a new design, build, test, and learn prediction cycle for metabolic engineering is proposed, for the design of efficient cell factories. This considers system‐wide characteristics and relies upon the integration of upstream (strain development), midstream (fermentation), and downstream (recovery and purification) analysis for strain design. In addition to this cycle, three issues should be taken into consideration: (i) The use of simple, available, and inexpensive materials; (ii) the identification and elimination of bottlenecks using non‐complex recovery and purification processes; (iii) the assessment of commercial and chemical industry requirements from the perspective of system efficiency. In this context, highly efficient microbial cell factories should be developed to produce compounds with improved production performance to meet industrial application requirements. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd

中文翻译：

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从工业副产品到增值化合物：通过系统代谢工程和生物过程的结合来设计高效的微生物细胞工厂

微生物细胞工厂已经通过经典的代谢工程方法被用于生产有价值的化合物，但这需要大量的时间和成本，以及劳动密集型的过程才能使细胞工厂具有工业竞争力。系统代谢工程是升级版，可将细胞理解为一个复杂的系统，其中连接了基因，转录本，蛋白质和代谢产物的网络，从而有助于分析潜在的细胞工厂。但是，针对工业规模生产的高效电池工厂设计需要一个综合系统，该系统不但要进行代谢，还要考虑工业生产方面的挑战。本文综述了系统生物学在代谢工程中的应用以及在扩大生物基化学生产规模的回收和纯化过程中的发展和挑战。然后，提出了用于代谢工程的新设计，构建，测试和学习预测周期，以用于高效细胞工厂的设计。这考虑了系统范围的特征，并依赖于上游（菌株开发），中游（发酵）和下游（回收和纯化）分析的集成来进行菌株设计。除这一周期外，还应考虑三个问题：（一）使用简单，可获得和廉价的材料；（ii）使用非复杂的回收和纯化过程识别和消除瓶颈；（iii）从系统效率的角度评估商业和化学工业的需求。在这种情况下，应该发展高效的微生物细胞工厂，以生产具有改善的生产性能的化合物，以满足工业应用需求。©2020年化学工业协会和John Wiley＆Sons，Ltd