Recent advances in metabolic engineering have enabled the production of chemicals via bio-conversion using microbes. However, downstream separation accounts for 60–80% of the total production cost in many cases. Previous work on microbial production of extracellular chemicals has been mainly restricted to microbiology, biochemistry, metabolomics, or techno-economic analysis for specific product examples such as succinic acid, xanthan gum, lycopene, etc. In these studies, microbial production and separation technologies were selected apriori without considering any competing alternatives. However, technology selection in downstream separation and purification processes can have a major impact on the overall costs, product recovery, and purity. To this end, we apply a superstructure optimization based framework that enables the identification of critical technologies and their associated parameters in the synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions. We divide extracellular chemicals into three categories based on their physical properties, such as water solubility, physical state, relative density, volatility, etc. We analyze three major extracellular product categories (insoluble light, insoluble heavy and soluble) in detail and provide suggestions for additional product categories through extension of our analysis framework. The proposed analysis and results provide significant insights for technology selection and enable streamlined decision making when faced with any microbial product that is released extracellularly. The parameter variability analysis for the product as well as the associated technologies and comparison with novel alternatives is a key feature which forms the basis for designing better bioseparation strategies that have potential for commercial scalability and can compete with traditional chemical production methods.

中文翻译：

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微生物转化产生的细胞外化学物质的分离过程的合成和分析

代谢工程学的最新进展使微生物能够通过生物转化来生产化学物质。但是，在许多情况下，下游分离占总生产成本的60-80％。以前有关细胞外化学物质微生物生产的研究主要限于微生物学，生物化学，代谢组学或特定产品实例的技术经济分析，例如琥珀酸，黄原胶，番茄红素等。在这些研究中，微生物生产和分离技术主要用于选择apriori，而不考虑任何竞争性替代方案。但是，下游分离和纯化过程中的技术选择可能会对总成本，产品回收率和纯度产生重大影响。为此，我们应用了基于上层结构优化的框架，该框架能够在合成和分析微生物转化产生的细胞外化学物质的分离过程中识别关键技术及其相关参数。根据其物理性质，例如水溶性，物理状态，相对密度，挥发性等，我们将细胞外化学物质分为三类。我们详细分析了三种主要的细胞外产物类别（不溶性轻质，不溶性重质和可溶性），并提供了建议。通过扩展我们的分析框架来增加其他产品类别。所提出的分析和结果为技术选择提供了重要的见识，并且当面对细胞外释放的任何微生物产品时，可以简化决策过程。