Amyris, Inc. 5885 Hollis St. Suite 100 Emeryville, CA, 94608, United States.
Amyris, Inc. 5885 Hollis St. Suite 100 Emeryville, CA, 94608, United States.
Metab Eng. 2021 Jan;63:102-125. doi: 10.1016/j.ymben.2020.09.004. Epub 2020 Oct 2.
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.
系统代谢工程面临着艰巨的任务，需要对微生物代谢进行重新布线，以便从各种廉价的原料中高效地生产出用于多种不同应用的高价值分子。由于这些细胞系统仍然过于复杂而无法准确建模，因此必须通过大量的反复试验和错误过程系统地创建和评估大量的工程生物体变体，以确定可用于生产的菌株。为了优化其可扩展的制造潜力，需要对菌株进行高通量筛选，这需要执行许多精心控制的、并行的、微型发酵过程，然后对复杂混合物进行高精度分析。这篇综述讨论了设计高通量、小规模发酵模型的策略，以预测在大规模商业生产中提高菌株性能的方法。本文介绍了来自工业界和学术界的成熟和有前途的方法，包括细胞培养和分析，主要侧重于微孔板和微流控筛选系统。
