الفهرس 
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Abstract
Marine sponges associated microorganisms are considered to be prolific source of bioactive natural products. Omics-based techniques such as metagenomics and metatranscriptomics have been used as effective tools to discover natural products. In this study, we used metagenomic analysis of Egyptian Red Sea sponges Hyrtios erectus and Phorbas topsenti microbiome along with an integrated metagenomic and metatranscriptomic analysis of the Red Sea sponge Theonella sp. to study the biodiversity and the biosynthetic activity of the Red Sea sponges to produce bioactive compounds.
Our data revealed high biodiversity of the three sponges’ microbiota with candidate phylum Poribacteria as the most dominant phylum in the microbial community of sponge Theonella sp. with an average of 27.5% while Proteobacteria was the most abundant phylum in sponges Hyrtios erectus and Phorbas topsenti microbiota with an average of 31% and 70% respectively. The analysis also revealed high biosynthetic potential of sponges Theonella sp. and Hyrtios erectus microbiome through detecting diverse types of biosynthetic gene clusters (BGCs) with predicted antibacterial, cytotoxic and inhibitory bioactivity. The majority of these BGCs were predicted to be novel as they did not show any similarity with any known cluster in the MIBiG database. Regarding Theonella sp., the sponge microbiota was found to have high biosynthetic activity as the majority of the detected clusters were found to be actively transcribed. The complete BGCs of the two cytotoxic theonellamide and misakinolide were detected in the Theonella sp. and found to be actively transcribed.