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High-throughput screening for high-efficiency small-molecule biosynthesis
Metabolic Engineering ( IF 6.8 ) Pub Date : 2020-10-02 , DOI: 10.1016/j.ymben.2020.09.004
Matthew Rienzo 1 , Shaina J Jackson 1 , Lawrence K Chao 1 , Timothy Leaf 1 , Thomas J Schmidt 1 , Adam H Navidi 1 , Dana C Nadler 1 , Maud Ohler 1 , Michael D Leavell 1
Affiliation  

Systems metabolic engineering faces the formidable task of rewiring microbial metabolism to cost-effectively generate high-value molecules from a variety of inexpensive feedstocks for many different applications. Because these cellular systems are still too complex to model accurately, vast collections of engineered organism variants must be systematically created and evaluated through an enormous trial-and-error process in order to identify a manufacturing-ready strain. The high-throughput screening of strains to optimize their scalable manufacturing potential requires execution of many carefully controlled, parallel, miniature fermentations, followed by high-precision analysis of the resulting complex mixtures. This review discusses strategies for the design of high-throughput, small-scale fermentation models to predict improved strain performance at large commercial scale. Established and promising approaches from industrial and academic groups are presented for both cell culture and analysis, with primary focus on microplate- and microfluidics-based screening systems.



中文翻译:

高效小分子生物合成的高通量筛选

系统代谢工程面临着重新连接微生物代谢的艰巨任务,以经济高效地从各种廉价原料中为许多不同应用生成高价值分子。由于这些细胞系统仍然太复杂而无法准确建模,因此必须通过大量试错过程系统地创建和评估大量工程生物变体,以识别可用于制造的菌株。菌株的高通量筛选以优化其可扩展的制造潜力需要执行许多精心控制的、平行的、微型发酵,然后对产生的复杂混合物进行高精度分析。这篇综述讨论了高通量设计的策略,小规模发酵模型来预测在大规模商业规模上提高的菌株性能。展示了来自工业和学术团体的成熟和有前途的方法,用于细胞培养和分析,主要关注基于微孔板和微流体的筛选系统。

更新日期:2020-10-02
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