构建高质量微生物天然产物库研究策略

Strategies on the construction of high-quality microbial natural product library—— A review

摘要:

微生物次级代谢产物历来是天然药物的重要来源，过去曾被称为“生物沙漠”的海洋，由于从中分离到大量新的微生物、基因及生物活性化合物，被重新认识逆转而成为一种“生物多样化的热带雨林”。构建一个高质量微生物库及其天然产物库是保证药物和其他筛选成功的前提和关键。但如何高效建立高质量微生物天然产物库仍面临很多瓶颈问题。我们拟从：（1）扩大可培养微生物的多样性及去重复化；（2）扩大基因资源多样性及去重复化；（3）扩大微生物次级代谢产物多样性及去重复化；（4）寻找崭新次级代谢产物的新技术新方法，特别是针对多靶位药物的高通量互动筛选方面提出应对的研究策略。利用上述化学微生物学策略分离生物活性化合物不仅在生物技术和制药学应用中显现重要性，也增加了我们对微生物的多样性、生态系统功能和应用生物学的理解。

Abstract:

The microbial secondary metabolites are always the main source of the natural drugs. The historical paradigm of the deep ocean as a biological ‘desert’ has shifted to one of a ‘rainforest’ owing to the isolation of many novel microbes and their associated bioactive compounds. A high quality microbial and its natural product library are crucial for successful drug and other screenings. However, how to build up the library efficiently is still faced with many bottlenecks. To overcome the difficulties and limitations, we reviewed the following strategies: (1) diversifying microbial sources and dereplication; (2) diversifying gene sources and dereplication; (3) diversifying microbial metabolite sources and dereplication; (4) novel methods and technologies for bioactive secondary metabolites, especially the high-throughput synergy screening for multi-target drugs. Bioactive compounds isolated using the above chemical microbiology strategies have not only shown importance in biotechnological and pharmaceutical applications but also increased our understanding of the diversity of microbe, ecosystem functions and the exploitable biology.