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

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Joseph Scott Zarins-Tutt, Tania Triscari Barberi, Hong Gao, Andrew Mearns-Spragg, Lixin Zhang, David Newman, Rebecca Jane Miriam Goss

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Abstract

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.
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Original languageEnglish
JournalNatural Product Reports
VolumeAdvance article
Early online date5 Nov 2015
DOIs
StatePublished - 2015

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