Insights into Red Sea Brine Pool Specialized Metabolism Gene Clusters Encoding Potential Metabolites for Biotechnological Applications and Extremophile Survival.

Laila Ziko,Rania Siam,Mustafa Adel,Mohamed N. Malash

doi:10.3390/md17050273

Laila Ziko, Rania Siam + Show 2 more

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https://doi.org/10.3390/md17050273

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Abstract

The recent rise in antibiotic and chemotherapeutic resistance necessitates the search for novel drugs. Potential therapeutics can be produced by specialized metabolism gene clusters (SMGCs). We mined for SMGCs in metagenomic samples from Atlantis II Deep, Discovery Deep and Kebrit Deep Red Sea brine pools. Shotgun sequence assembly and secondary metabolite analysis shell (antiSMASH) screening unraveled 2751 Red Sea brine SMGCs, pertaining to 28 classes. Predicted categorization of the SMGC products included those (1) commonly abundant in microbes (saccharides, fatty acids, aryl polyenes, acyl-homoserine lactones), (2) with antibacterial and/or anticancer effects (terpenes, ribosomal peptides, non-ribosomal peptides, polyketides, phosphonates) and (3) with miscellaneous roles conferring adaptation to the environment/special structure/unknown function (polyunsaturated fatty acids, ectoine, ladderane, others). Saccharide (80.49%) and putative (7.46%) SMGCs were the most abundant. Selected Red Sea brine pool sites had distinct SMGC profiles, e.g., for bacteriocins and ectoine. Top promising candidates, SMs with pharmaceutical applications, were addressed. Prolific SM-producing phyla (Proteobacteria, Actinobacteria, Cyanobacteria), were ubiquitously detected. Sites harboring the largest numbers of bacterial and archaeal phyla, had the most SMGCs. Our results suggest that the Red Sea brine niche constitutes a rich biological mine, with the predicted SMs aiding extremophile survival and adaptation.

Highlights

In the era of antibiotic resistance and a concern for a post-antibiotic era there is a pressing need to combat resistance and discover novel antibiotics [1,2,3]
In order to eliminate the effects of assembly size bias in downstream analyses, the number of assembled reads for each site was used to normalize the number of detected specialized metabolism gene clusters (SMGCs) (Table 1)
We identified a subset of SMGCs common in brine pool water samples and distinct from the sediment samples and the overlying water column

Summary

Introduction

In the era of antibiotic resistance and a concern for a post-antibiotic era there is a pressing need to combat resistance and discover novel antibiotics [1,2,3]. In the USA alone, around 2 million people a year acquire a bacterial infection that is resistant to all available antibiotics [4]. Anticancer chemotherapeutic resistance is another recent biomedical challenge, which arises either intrinsically or extrinsically, following therapy [5]. It is a necessity to search for new chemotherapeutics [3,4,5]. Nature is considered a mine to explore for small molecules, which may be used as new therapeutic drug leads. Until 2014, a large portion of the rising number of drugs was attributed to natural products [6]. Many organisms and microbes produce specialized metabolites that have a plethora

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