基于大片段克隆技术的活性天然产物研究进展

Advances in the Discovery of Active Natural Products by Large Fragment Cloning

摘要:

活性天然产物具有多样的结构和活性，可作为小分子药物的主要来源。随着多重耐药菌和超级细菌的出现，迫切需要开发新型的活性天然产物。大片段克隆技术是近年来发现活性天然产物的重要手段，在获取活性天然产物生物合成基因簇方面展现出明显优势，结合高效的基因簇靶向筛选方法，显著加速了活性天然产物的发现。作者对各类活性天然产物进行了分类概述，随后对多种大片段克隆技术如人工染色体技术、Red/ET重组系统、TAR技术耦合CRISPR-Cas9系统进行了详细阐述，对不同类型技术的优缺点及应用范围进行了对比并展望了其未来前景，为活性天然产物的研发提供理论指导。

Abstract:

Active natural products have diverse structures and activities and can be a major source of small molecule drugs. Given the emergence of multi-drug resistant bacteria and superbacteria, there is an urgent need to develop new active natural products. Large fragment cloning has been an important tool for the discovery of active natural products in recent years, and it has demonstrated obvious advantages in obtaining the biosynthetic gene clusters of active natural products. This approach, combined with efficient cluster-targeted screening methods, has significantly accelerated the discovery of active natural products. This review summarizes a wide variety of active natural products. Furthermore, this paper elaborates on the principles and applications of several large fragment cloning technologies, including artificial chromosome technology, Red/ET recombination system, and TAR technology coupled with the CRISPR-Cas9 system. This paper compares the advantages, disadvantages, and application scopes of different technologies and envisions their future prospects, aiming to provide theoretical guidance for the research and development of active natural products.