Advances in strategies for activating silent biosynthetic gene clusters in<i> Streptomyces</i>

DAI Yan; WU Xuri; CHEN Yijun

doi:10.11665/j.issn.1000-5048.20190401

Journal of China Pharmaceutical University > 2019 > 50(4): 379-388. > DOI: 10.11665/j.issn.1000-5048.20190401

DAI Yan, WU Xuri, CHEN Yijun. Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces[J]. Journal of China Pharmaceutical University, 2019, 50(4): 379-388. DOI: 10.11665/j.issn.1000-5048.20190401

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Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces

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Abstract

Microbial secondary metabolites have always been one of the important sources of discovery and development of new drugs due to their remarkable biological activities. The explosion of genome sequences has revealed that Streptomyces harbor an immensely untapped biosynthetic potential. However, the number of active secondary metabolites with new skeletons or structural units found from Streptomyces is much lower than that of biosynthetic gene clusters(BGCs), mainly due to the fact that many BGCs are either expressed weakly or transcriptionally silent under conventional laboratory conditions. Beginning with the bioinformatics tools for BGCs prediction, this review focuses on the classical approaches to activate silent BGCs of Streptomyces in native and heterologous hosts. Moreover, several new strategies including transcriptional factors decoy, reporter-guided high-throughput selection and muliplexed CRISPR-TAR were detailed, which provide methodological references for mining new secondary metabolites from Streptomyces.
- Streptomyces,
- secondary metabolites,
- silent biosynthetic gene clusters,
- bioinformatic tools,
- gene clusters activation strategies

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