COSMos · Chemistry of Sponge Microbiomes

Chemistry of Sponge Microbiomes

Molecules made by nature, or natural products, inspire the majority of currently approved small molecules for use in medicine. With an increase in widespread antibiotic resistance and the perpetual search for anticancer drugs, new sources of natural products must be discovered. The marine environment is a proven, prolific source of novel bioactive molecules and much of the ocean remains chemically and genetically unexplored. The mesophotic zone, where light barely reaches the ocean floor, is particularly neglected because of the technological difficulty of reaching this twilight zone of the ocean. Shallow water marine sponges have been well documented to have diverse microbial populations and impressive chemical repertoires. Mesophotic sponges, however, are relatively unstudied in terms of their natural product potential. This project aimed to take a deep dive into the metagenomes of mesophotic sponges for their natural product potential. Hybrid sequencing and assembly of metagenomes of five prioritized sponges yielded 435 medium to high quality metagenome assembled genomes (MAGs), each representing the first glimpse into uncultured sponge symbionts and their metabolic capacities. Within the metagenomes and MAGs, thousands of biosynthetic gene clusters (BGCs) were identified, the vast majority of which are novel, with less than 1% of BGC families containing a known BGC from a curated database. BGC networking revealed one BGC family that is highly similar to a characterized ether lipid producing BGC. There are multiple putative ether lipid BGC families in our sponge metagenomes, which are found in both Acidobacteria and Poribacteria MAGs. One of these putative ether lipid BGCs was cloned in E. coli and successful expression of each gene in the BGC was determined using RT-PCR. Current work is exploring whether the heterologous host with the ether lipid-like BGC can actually produce ether lipids. To go beyond easily annotated BGCs, we also used non-standard genome mining methods to identify non-canonical BGCs harboring putative halogenases, resulting in an interesting family of BGCs residing in related Acidobacteria MAGs from shallow, mesophotic and deep sea sponges. Continuing efforts are aimed at heterologously expressing these cryptic BGCs in the lab to confirm our bioinformatic findings. Overall, this project revealed the identity and metabolic capacities of hundreds of uncultured mesophotic sponge symbionts and spurred two heterologous expression efforts.

Data: CORDIS, © European Union