Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products

被引:93
作者
Zarins-Tutt, Joseph Scott [1 ]
Barberi, Tania Triscari [1 ]
Gao, Hong [1 ]
Mearns-Spragg, Andrew [2 ]
Zhang, Lixin [3 ]
Newman, David J. [4 ]
Goss, Rebecca Jane Miriam [1 ]
机构
[1] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Scotland
[2] Aquapharm Biodiscovery Ltd, European Ctr Marine Biotechnol, Oban PA37 1QA, Argyll, Scotland
[3] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China
[4] Frederick Natl Labs Canc Res, Nat Prod Branch, Frederick, MD 21702 USA
关键词
STREPTOMYCES-COELICOLOR A3(2); NONRIBOSOMAL PEPTIDE SYNTHETASE; CPK GENE-CLUSTER; ANTIBIOTIC PRODUCTION; HETEROLOGOUS EXPRESSION; SUBINHIBITORY CONCENTRATIONS; SECONDARY METABOLITES; GENOME SEQUENCE; POLYKETIDE SYNTHASES; SIGNALING MOLECULES;
D O I
10.1039/c5np00111k
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Over the centuries, microbial secondary metabolites have played a central role in the treatment of human diseases and have revolutionised the pharmaceutical industry. With the increasing number of sequenced microbial genomes revealing a plethora of novel biosynthetic genes, natural product drug discovery is entering an exciting second golden age. Here, we provide a concise overview as an introductory guide to the main methods employed to unlock or up-regulate these so called 'cryptic', 'silent' and 'orphan' gene clusters, and increase the production of the encoded natural product. With a predominant focus on bacterial natural products we will discuss the importance of the bioinformatics approach for genome mining, the use of first different and simple culturing techniques and then the application of genetic engineering to unlock the microbial treasure trove.
引用
收藏
页码:54 / 72
页数:19
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