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The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms

1
BIOMERIT Research Centre, School of Microbiology, University College Cork—National University of Ireland, Cork, Ireland
2
School of Microbiology, University College Cork—National University of Ireland, Cork, Ireland
3
School of Biomedical Sciences, Curtin University, Perth WA 6845, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Proksch
Mar. Drugs 2015, 13(8), 4754-4783; https://doi.org/10.3390/md13084754
Received: 5 June 2015 / Revised: 5 June 2015 / Accepted: 27 July 2015 / Published: 31 July 2015
Unlocking the rich harvest of marine microbial ecosystems has the potential to both safeguard the existence of our species for the future, while also presenting significant lifestyle benefits for commercial gain. However, while significant advances have been made in the field of marine biodiscovery, leading to the introduction of new classes of therapeutics for clinical medicine, cosmetics and industrial products, much of what this natural ecosystem has to offer is locked in, and essentially hidden from our screening methods. Releasing this silent potential represents a significant technological challenge, the key to which is a comprehensive understanding of what controls these systems. Heterologous expression systems have been successful in awakening a number of these cryptic marine biosynthetic gene clusters (BGCs). However, this approach is limited by the typically large size of the encoding sequences. More recently, focus has shifted to the regulatory proteins associated with each BGC, many of which are signal responsive raising the possibility of exogenous activation. Abundant among these are the LysR-type family of transcriptional regulators, which are known to control production of microbial aromatic systems. Although the environmental signals that activate these regulatory systems remain unknown, it offers the exciting possibility of evoking mimic molecules and synthetic expression systems to drive production of potentially novel natural products in microorganisms. Success in this field has the potential to provide a quantum leap forward in medical and industrial bio-product development. To achieve these new endpoints, it is clear that the integrated efforts of bioinformaticians and natural product chemists will be required as we strive to uncover new and potentially unique structures from silent or cryptic marine gene clusters. View Full-Text
Keywords: silent; cryptic; bioactive gene clusters; polyketide synthases; non-ribosomal peptide synthases; metagenomics; heterologous expression silent; cryptic; bioactive gene clusters; polyketide synthases; non-ribosomal peptide synthases; metagenomics; heterologous expression
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Reen, F.J.; Romano, S.; Dobson, A.D.W.; O'Gara, F. The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms. Mar. Drugs 2015, 13, 4754-4783.

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