摘要
噬菌体,以杀菌特性而闻名的天然病毒,是地球上多样性和丰度最高的生物体。在过去100多年中,噬菌体的研究极大地推动了遗传学、分子生物学和合成生物学的发展。随着耐药超级细菌的流行,噬菌体疗法引人入胜的科学历史也被广为传颂。然而,相对于自然环境中丰富的噬菌体数量(总数为10^(31),比所有其他生物的总和还要多),目前只有少数噬菌体成功应用于对抗耐药性细菌感染及其他工程领域。当前,急需践行合成生物学从“造物致知”到“造物致用”理念,采用高通量测序和基因组精准编辑等先进生物技术来创建具有独特属性的增强变体,提高噬菌体治疗的疗效和可编程性。本文综述了近年来噬菌体基因工程改造方法的技术进展以及合成生物学助力噬菌体应用技术发展的研究动态,如按照实际需求改造噬菌体宿主范围、借助宏基因组挖掘自然界中噬菌体的广泛资源、结合多组学技术揭示噬菌体与宿主互作的分子机制、调控肠道噬菌体组维持肠道稳态以促进人体健康及利用大数据和新型人工智能指导噬菌体理性设计。总之,合成生物学正在跨时代驱动传统实验研究范式转变,结合“设计—构建—测试—学习(DBTL)循环”理性设计目标噬菌体,无论是自上而下的体系优化,还是自下而上的生命体重构,工程噬菌体的合成生物学“智造”都大有可为。
Bacteriophages(phages),natural viruses known for infecting and killing bacteria,are the most diverse and abundant organisms on Earth.Within the past 100 years of research on phages,breakthroughs in genetics,molecular biology,and synthetic biology have been successfully achieved.The fascinating scientific history of phage therapy has been repeatedly reported,as drug-resistant bacteria are becoming increasingly prevalent.Although phages outnumber other species combined in nature(10^(31) in total),only a small fraction of them have been successfully exploited for fighting infections caused by drug-resistant bacteria.Therefore,there is an urgent need for implementing the motto of synthetic biology,“build to learn,build to use”,and also using methods such as high-throughput sequencing and precise genome editing to create enhanced variants with unique features,improving efficacy and programmability for phage therapy.In the review,we discuss recent technological advances in phage genome engineering approaches and the potential applications of synthetic biology to engineer phages,such as modifying the host range of phages for practical needs,mining the extensive resources of phages in nature with the help of macro genomes,combining multi-omics technologies to reveal molecular mechanisms underlying phage-host interactions,regulating intestinal phages to maintain intestinal homeostasis for human health,and using big data and artificial intelligence to guide rational phage design.Synthetic biology is driving a paradigm shift in traditional experimental research by combining“Design-Build-Test-Learn(DBTL)cycles”to rational design for phages,making synthetically designed phages promising for both top-down system optimization and bottom-up life-form reconstruction.
作者
陈青黎
童贻刚
CHEN Qingli;TONG Yigang(College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China)
出处
《合成生物学》
CSCD
2023年第2期283-300,共18页
Synthetic Biology Journal
基金
国家自然科学基金(32001834)
国家重点研发计划(2018Y FA 0903000)
军事生物安全研究计划(20SWAQX27)。
