高通量筛选系统在定向改造中的新进展  

Advances of high-throughput screening system in reengineering of biological entities

作　　者：杨建花 苏晓岚 朱蕾蕾 Jianhua Yang;Xiaolan Su;Leilei Zhu(Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China;University of Science and Technology of China,Hefei 230026,Anhui,China)

机构地区：[1]中国科学院天津工业生物技术研究所,天津300308 [2]中国科学技术大学,安徽合肥230026

出　　处：《生物工程学报》2021年第7期2197-2210,共14页Chinese Journal of Biotechnology

基　　金：国家自然科学基金(No.21708046);天津市自然科学基金(No.19JCYBJC24300);天津市合成生物技术创新能力提升行动(No.TSBICIP-KJGG-006)资助。

摘　　要：酶和细胞工厂是工业生物技术的核心,在医药、化工、食品、农业、能源等诸多领域发挥重要作用。一般天然酶和细胞均需通过分子改造提高其催化效率、稳定性及立体选择性等。定向改造为快速改善酶和细胞工厂的性能提供了可能性,其中灵敏可靠的高通量筛选方法是决定酶和细胞工厂成功高效定向改造的关键。文中阐述并分析讨论了各种筛选方法的优缺点、适用范围以及信号产生策略,并总结了近3年超高通量筛选技术在酶和细胞工厂定向改造中的最新研究进展。在此基础上,讨论了高通量筛选系统目前面临的限制性因素,并对高通量筛选方法未来的发展趋势作出了展望。希望生物技术和仪器开发等各领域的研究者能够紧密合作,实现协同发展,进一步提升高通量筛选技术的可靠性和适用性。Enzymes and cell factories are the core of industrial biotechnology. They play important roles in various fields such as medicine, chemical industry, food, agriculture, and energy. Usually, natural enzymes and cells need to be engineered to improve the catalytic efficiency, stability and enantioselectivity. Directed evolution makes it possible to rapidly improve the properties of enzymes and cell factories. Sensitive and reliable high-throughput screening approaches are the key for successful and efficient engineering of enzymes and cell factories. In this review, we first summarize the advantages and disadvantages of different screening methods and signal generation strategies as well as their application scope;we then describe the latest advances of ultra-high throughput screening technology applied in the directed evolution of enzymes and cell factories in the past three years. On this basis, we discuss the limiting factors that need to be further improved for high-throughput screening systems and forecast the future development trends of high-throughput screening methods, hoping that researchers in various fields including biotechnology and instrument development can cooperate closely to enhance the reliability and applicability of the high-throughput screening techniques.

关 键 词：高通量筛选 定向进化 酶 细胞工厂 荧光激活细胞分选 液滴微流控分选 

分 类 号：Q814.9[生物学—生物工程]