微生物次级代谢产物多样性发掘方法  

Methods for exploring the chemical diversity of microbial secondary metabolites

作　　者：方岫琴 王文璟 李华东 张晓婷 朱天骄[1] 车茜[1] 李德海[1,2] 张国建 Fang Xiuqin;Wang Wenjing;Li Huadong;Zhang Xiaoting;Zhu Tianjiao;Che Qian;Li Dehai;Zhang Guojian(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003;Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237;Marine Biomedical Research Institute of Qingdao,Qingdao 266100)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,医药学院,青岛266003 [2]崂山实验室海洋药物和生物制品功能实验室,青岛266237 [3]青岛海洋生物医药研究院,青岛266100

出　　处：《中国抗生素杂志》2024年第4期415-426,共12页Chinese Journal of Antibiotics

基　　金：国家自然科学基金面上项目(No.41976105);山东省泰山学者青年专家项目(No.tsqn202103153)。

摘　　要：微生物次级代谢产物是微生物在生长过程中产生的非必需性代谢产物,其往往具有独特的生物活性。随着对微生物次级代谢产物多样性研究的不断深入开展,研究者逐渐发现在实验室的常规培养条件下微生物的代谢潜能不能完全被激发,从中可获得的天然产物结构类型远远少于其代谢潜能所决定的数量。近年来,随着基因组技术、分子生物学技术特别是合成生物学相关技术的发展,研究人员开发了如OSMAC、表观遗传、异源表达等多种方法,从多个角度多层次地发掘次级代谢产物多样性。这些方法有效激活潜在的生物合成基因簇、提高了微生物次级代谢产物多样性,加之与高通量筛选方法联合应用,能够显著改善了微生物活性天然产物的发现效率。本文综述了微生物次级代谢潜能的激活以及代谢产物高效筛选的方法和技术,为提高微生物次级代谢产物多样性发掘,加快先导化合物的发现提供参考。Microbial secondary metabolites are non-essential metabolites created by microorganisms throughout the development process,but they frequently exhibit unique biological activities.As research on microbial natural products went on,researchers gradually found that the metabolic capacity of microorganisms could not be completely activated under normal laboratory growth conditions,which led to the fact that the skeletal diversities of natural products obtained from some microbial strains were significantly less than the amount indicated by their potential metabolic capacity.With recent years'development in genomic technology and molecular biology technology,especially synthetic biology-related technologies,several advanced approaches,including OSMAC,epigenetic expression and heterologous expression,have been applied to investigate the diversity of secondary metabolites at the multi-angle and multi-level.Combined with proper screening techniques,those above methods showed increased efficiency in activating silent biosynthetic gene clusters and obtaining diversified secondary metabolites from microbial strains.This article reviewed practical methodologies and strategies for tapping up microbial metabolic potential and screening unique metabolites to provide references for efficiently exploring the variety of microbial natural products and speeding up the identification of drug lead compounds.

关 键 词：微生物次级代谢产物 沉默基因簇 代谢潜能 激活 结构多样性 

分 类 号：R978.1[医药卫生—药品]