利用合成生物学技术深入挖掘放线菌中活性次级代谢产物

Bioprospecting secondary metabolites of actinomycetes through synthetic biology

摘要:

放线菌是一类能够产生丰富生物小分子药物的微生物, 对人类的健康事业做出了杰出的贡献。但近几十年来, 来源于微生物并最终上市的药物越来越少, 而病原菌的抗药性问题却越发严重, 人们对新药的期待越来越迫切。本文介绍了近十年里发展迅速的合成生物学对微生物次级代谢产物研发的促进作用。合成生物学以工程化的思想对生命系统进行设计与改造, 使传统方法难以获取的放线菌次级代谢产物通过外源宿主得以产生, 充分利用了自然界的资源; 此外, 对次级代谢基因簇的合理设计和对生物元件的应用不仅使人们获得了自然界中原本不存在的新化合物, 还能使某些具有广泛应用价值药物的产量得以显著提高; 最后, 还介绍了合成生物学领域近些年DNA组装的新技术和新方法, 为从事次级代谢产物研发的工作者提供便利。

Abstract:

Actinobacteria are a class of microorganisms that can produce plenty of bioactive small molecule drugs, making an outstanding contribution to the human health. During the past decades, microorganisms derived and eventually marketed drugs become fewer and fewer, in the meanwhile, the problem caused by drug resistance pathogens become more and more serious, so people look forward to the new drugs urgently. Synthetic biology, which is developing fast in the past 10 years, plays an important role in the research and development of secondary metabolites. The biosystem is designed and rebuilt under the guidance of engineering science, from which the indiscoverable secondary metabolites can be obtained through heterologous expression. What is more, the rational designed gene cluster and the utilization of bio-elements lead to the new compounds that do not exist in nature as well as yield improved strains. The new techniques and methods of DNA assembly are also introduced, which make convenience to the researchers on secondary metabolites.