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Triggers and cues that activate antibiotic production by actinomycetes

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Journal of Industrial Microbiology & Biotechnology

Abstract

Actinomycetes are a rich source of natural products, and these mycelial bacteria produce the majority of the known antibiotics. The increasing difficulty to find new drugs via high-throughput screening has led to a decline in antibiotic research, while infectious diseases associated with multidrug resistance are spreading rapidly. Here we review new approaches and ideas that are currently being developed to increase our chances of finding novel antimicrobials, with focus on genetic, chemical, and ecological methods to elicit the expression of biosynthetic gene clusters. The genome sequencing revolution identified numerous gene clusters for natural products in actinomycetes, associated with a potentially huge reservoir of unknown molecules, and prioritizing them is a major challenge for in silico screening-based approaches. Some antibiotics are likely only expressed under very specific conditions, such as interaction with other microbes, which explains the renewed interest in soil and marine ecology. The identification of new gene clusters, as well as chemical elicitors and culturing conditions that activate their expression, should allow scientists to reinforce their efforts to find the necessary novel antimicrobial drugs.

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Acknowledgments

We are grateful to Young Choi for drawing chemical structures, to Geneviève Girard for comments on the manuscript, and to Kenneth McDowall, Marnix Medema and Michael Fischbach for sharing unpublished data. The work was supported by a CSC PhD fellowship from the Chinese government to HZ and by grant 10467 from the Netherlands Technology Foundation STW to GPvW.

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  1. Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, The Netherlands

    Hua Zhu, Stephanie K. Sandiford & Gilles P. van Wezel

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  1. Hua Zhu
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Correspondence to Gilles P. van Wezel.

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Zhu, H., Sandiford, S.K. & van Wezel, G.P. Triggers and cues that activate antibiotic production by actinomycetes. J Ind Microbiol Biotechnol 41, 371–386 (2014). https://doi.org/10.1007/s10295-013-1309-z

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