生物设施平台及其工业应用

doi:10.12211/2096-8280.2023-024

合成生物学 ›› 2023, Vol. 4 ›› Issue (5): 892-903.DOI: 10.12211/2096-8280.2023-024

生物设施平台及其工业应用

赵国淼¹^,², 杨鑫¹^,², 张媛¹^,², 王靖¹^,², 谭剑¹^,², 魏超¹^,², 周娜娜¹^,², 李凡¹^,², 王小艳¹^,²

^1.中粮营养健康研究院有限公司，北京 102209
^2.营养健康与食品安全北京市重点实验室，北京 102209

收稿日期:2023-03-17 修回日期:2023-05-08 出版日期:2023-10-31 发布日期:2023-11-15
通讯作者: 王小艳
作者简介:赵国淼（1989—），男，博士，工程师。研究方向为工业微生物改造与高通量筛选、计算生物学与生物信息学。E-mail：zhaoguomiao@cofco.com
王小艳（1980—），女，博士，正高级工程师。研究方向围绕淀粉质原料生物加工过程工业菌株和酶制剂的开发，主要聚焦生物燃料乙醇、生物基材料、功能糖等领域。E-mail：wangxiaoyan@cofco.com
基金资助:
国家重点研发计划“合成生物学”重点专项，合成生物学自动化铸造平台关键技术研发(2018YFA0902900)

Biofoundry and its industrial application

Guomiao ZHAO¹^,², Xin YANG¹^,², Yuan ZHANG¹^,², Jing WANG¹^,², Jian TAN¹^,², Chao WEI¹^,², Nana ZHOU¹^,², Fan LI¹^,², Xiaoyan WANG¹^,²

^1.Nutrition & Health Research Institute，COFCO Corporation，Beijing 102209，China
^2.Beijing Key Laboratory of Nutrition，Health and Food Safety，Beijing 102209，China

Received:2023-03-17 Revised:2023-05-08 Online:2023-10-31 Published:2023-11-15
Contact: Xiaoyan WANG

摘要/Abstract

摘要：

传统菌株改造和筛选实验存在操作烦琐、耗时、易错、难以规模化等问题，生物设施平台将自动化、机器人技术、数据分析与生物研究相结合，通过导轨和机械手臂实现自动化操作，提高了实验操作的稳定性，通过缩小培养体积（微孔板或微液滴），提高了培养和筛选通量，解决了上述问题，大大提高了研发效率。本文简单介绍了自动化设施平台的发展和常见的高通量检测方法，重点介绍了中粮营养健康研究院的自动化设施平台，并结合开展的项目叙述了平台在生物燃料菌株开发、传统酿造菌株筛选、酶的定向进化和筛选等领域的应用，可以预见自动化和高通量化在菌株改造和筛选方向巨大的应用价值。实验室自动化是涉及机械工程、自动化、计算机和生命科学等学科的交叉领域，需要各方面共同努力，才能推动实验室向更高程度的自动化和智能化方向发展。

关键词: 生物设施平台, 自动化, 高通量筛选, 菌株改造, 工业微生物

Abstract:

Traditional methods for strain isolation and improvement can be cumbersome, time-consuming, error-prone, and difficult to scale up, leading to inefficiencies in research and development workflows. With the integration of automation and robotics technology, biofoundry can achieve automated operations through guide rails and robotic arms, leading to improved stability and precision of experimental operations. Additionally, by utilizing smaller cultivation volumes, such as microplates or droplets, the cultivation and screening throughput can be increased, addressing the currently existing issues of traditional methods. This can greatly improve research and development efficiency, allowing for the testing and optimization of large numbers of microbial strains or genetic variants in a high-throughput manner. The biofoundry encompasses interdisciplinary fields such as mechanical engineering, automation, computer science, and life sciences. The collaboration among these fields is crucial for the development and advancement of laboratory automation. By leveraging automation and high-throughput technologies, the field of strain isolation and improvement can benefit from increased efficiency, improved reliability, and scalability. These advancements can accelerate the progress of microbial strain engineering for various applications in biotechnology, medicine, agriculture, and energy production. This paper briefly introduces the composition and classification of the biofoundry, the high-throughput detection method, and focuses on the high-throughput screening platform built by the research team from Nutrition & Health Research Institute, COFCO. In combination with the projects carried out, it introduces the application of the high-throughput screening platform in the fields of biofuel strain development, traditional brewing strain screening, feed substitute antimicrobial screening, directed evolution and screening of enzymes, etc.

Key words: biofoundry, automation, high-throughput screening, strain improvement, industrial microorganism

中图分类号:

Q819

赵国淼, 杨鑫, 张媛, 王靖, 谭剑, 魏超, 周娜娜, 李凡, 王小艳. 生物设施平台及其工业应用[J]. 合成生物学, 2023, 4(5): 892-903.

Guomiao ZHAO, Xin YANG, Yuan ZHANG, Jing WANG, Jian TAN, Chao WEI, Nana ZHOU, Fan LI, Xiaoyan WANG. Biofoundry and its industrial application[J]. Synthetic Biology Journal, 2023, 4(5): 892-903.

图/表 7

图1 伊利诺伊大学的自动化实验室iBioFAB平台（https：//www.igb.illinois.edu/iBIOFAB）

Fig.1 Illinois Biological Foundry for Advanced Biomanufacturing (iBioFAB)

图2 中粮营养健康研究院自动化设施平台

Fig. 2 Automated biofoundry at COFCO

表1 三种筛选方法对比

Table 1 Comparison of three screening methods

筛选方法	检测信号	灵敏度	通量
MTP^[48]	吸光度和荧光强度	一般	10⁶个/天
FACS^[49]	荧光强度	高	10⁸个/时
DMF^[50]	荧光强度、拉曼光谱、吸光度、质谱	高	10⁸个/天

图3 工业酿酒酵母的多重胁迫耐受性改造

Fig.3 Improvement of Saccharomyces cerevisiae for multiple stress tolerance

图4 高通量平台在传统菌株筛选中的应用

Fig. 4 Application of high-throughput platform in traditional strain screening

图5 生物设施平台EUGT11酶定向进化和筛选中的应用

Fig. 5 Application of the biofoundry in directed evolution and screening of EUGT11

图6 生物设施平台在真菌毒素降解酶定向进化和筛选中的应用

Fig. 6 Application of biofoundry in directed evolution and screening of mycotoxins degrading enzymes

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生物设施平台及其工业应用

Biofoundry and its industrial application

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