自动化高通量技术在天然产物生物合成中的应用  

Application of automated high-throughput technology in natural product biosynthesis

作　　者：胡哲辉 徐娟[2] 卞光凯 HU Zhehui;XU Juan;BIAN Guangkai(Insititute of Syntheitc Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,Guangdong,China;National Key Laboeratory for Germplasm Innovation&Utilization of Horticultural Crops,College of Horticulture and Forestry,Huazhong Agricultural University,Wuhan 430071,Hubei,China)

机构地区：[1]中国科学院深圳先进技术研究院合成生物学研究所,广东深圳518055 [2]华中农业大学园艺林学学院,果蔬园艺作物种质创新与利用全国重点实验室,湖北武汉430071

出　　处：《合成生物学》2023年第5期932-946,共15页Synthetic Biology Journal

基　　金：国家重点研发计划“绿色生物制造”重点专项(2022YFC2106100,2021YFC2102600);国家自然科学基金面上项目(32070063)。

摘　　要：天然产物与人们的日常生活息息相关,是药物、食品、营养添加剂、色素、化妆品等产品的重要来源。发掘新的天然产物并实现其高效合成对于提升人们的生活水平至关重要。然而,研究通量低和产物产量低已成为限制该领域快速发展的两大瓶颈。为了克服这些问题,自动化高通量技术的引入在天然产物生物合成领域具有重要意义。该技术可以将高度依赖人力资源的低通量和随机性手工操作的实验过程转变为基于先进设备的自动化、标准化和高效的研究过程。因此,将自动化高通量技术引入天然产物生物合成领域可以有效解决研究瓶颈,加速研发进程。本文综述了自动化高通量技术在天然产物生物合成领域的应用,阐述了其在天然产物挖掘、高效生物合成和快速检测等方面的优势。最后,讨论了该技术现存缺陷,包括仪器设备造价高昂、操作复杂,并且一些装置尚未得到推广。相信在合成生物、信息技术、自动化等多领域的共同协作下,自动化高通量技术具备的独特优势将为新型天然产物功能产品的开发提供可持续来源。Natural products are usually secondary metabolites derived from animals,plants,or microorganisms.They are closely related to people's daily lives and important sources of drugs,food and nutrition additives,pigments,and cosmetics.The exploration of novel natural products and the efficient synthesis of value-added products are key to enriching and improving people's living standards.Researchers have exploited a large number of natural products through strategies such as direct product isolation,homologous activation,and heterologous expression.However,low throughput and low titer have become the two major bottlenecks of this field.With the rapid development of synthetic biology,automated high-throughput technology has been developed to transform the low throughput,stochastic manual experimental process that relies on human resources into an automated,standardized,and efficient research process,which is regarded as a leading technology in natural product biosynthesis.This review compares and highlights the advantages of automated high-throughput technology over the traditional techniques within the context of natural products biosynthesis,provides an overview of the components and principles of automated high-throughput workstations,and summarizes the existing and upcoming automated high-throughput facilities.In addition,this review highlights the applications of automated high-throughput technology,including the batch mining of natural product biosynthetic genes and gene clusters,overproduction,and efficient detection of value-added natural products.These examples effectively illustrate the benefits of this technology in the field of natural product biosynthesis.In conclusion,the use of automated high-throughput technology in synthetic biology has shown promising results,particularly in the high-throughput discovery and biosynthesis of natural products.Finally,we discuss the existing shortcomings of the technology.Despite the cost and operational challenges associated with the automated high-throughput technology,i

关 键 词：合成生物学 天然产物 自动化技术 高产底盘 生物铸造 

分 类 号：Q816[生物学—生物工程]