Discovery of microbial natural products by activation of silent biosynthetic gene clusters

被引:656
|
作者
Rutledge, Peter J. [1 ]
Challis, Gregory L. [2 ]
机构
[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia
[2] Univ Warwick, Dept Chem, Coventry CV4 7AL, W Midlands, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
STREPTOMYCES-COELICOLOR GENOME; SECONDARY METABOLISM; ANTIBIOTIC PRODUCTION; POLYKETIDE SYNTHASES; MASS-SPECTROMETRY; CRYPTIC POLYKETIDE; DRIVEN DISCOVERY; RARE-EARTH; PEPTIDE; BACTERIAL;
D O I
10.1038/nrmicro3496
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities and a wide variety of applications in medicine and agriculture, such as the treatment of infectious diseases and cancer, and the prevention of crop damage. Genomics has revealed that many microorganisms have far greater potential to produce specialized metabolites than was thought from classic bioactivity screens; however, realizing this potential has been hampered by the fact that many specialized metabolite biosynthetic gene clusters (BGCs) are not expressed in laboratory cultures. In this Review, we discuss the strategies that have been developed in bacteria and fungi to identify and induce the expression of such silent BGCs, and we briefly summarize methods for the isolation and structural characterization of their metabolic products.
引用
收藏
页码:509 / 523
页数:15
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