Mass Spectrometry-Based Integration and Expansion of the Chemical Diversity Harbored Within a Marine Sponge

Abstract

Marine sponges and their associated symbionts produce a structurally diverse and complex set of natural products including alkaloids, terpenoids, peptides, lipids, and steroids. A single sponge with its symbionts can produce all of the above-mentioned classes of molecules and their analogs. Most approaches to evaluating sponge chemical diversity have focused on major metabolites that can be isolated and characterized; therefore, a comprehensive evaluation of intra- (within a molecular family; analogs) and inter-chemical diversity within a single sponge remains incomplete. We use a combination of metabolomics tools, including a supervised approach via manual library search and literature search, and an unsupervised approach via molecular networking and MS2LDA analysis to describe the intra and inter-chemical diversity present in Smenospongia aurea. Furthermore, we use imaging mass spectrometry to link this chemical diversity to either the sponge or the associated cyanobacteria. Using these approaches, we identify 7 more molecular features that represent analogs of four previously known peptide/polyketide smenamides and assign the biosynthesis of these molecules to the symbiotic cyanobacteria by imaging mass spectrometry. We extend this analysis to a wide diversity of molecular classes including indole alkaloids and meroterpenes.

Multi-Omic Profiling of Melophlus Sponges Reveals Diverse Metabolomic and Microbiome Architectures that Are Non-overlapping with Ecological Neighbors

“…The rules that govern Melophlus sponges' preponderance towards glycosylated natural products while Lamellodysidea sponges select for polyhalogenated phenols are presently not clear. These two examples are in complete contrast to our metabolomic description of the Floridian sponge Smenospongia aurea, the metabolome of which, while being very diverse, is not enriched in one particular natural product class [49].…”

Fast Detection of Two Smenamide Family Members Using Molecular Networking

“…Two smenamide-related clusters were present in the network and are shown in Figure 2. Cluster 1 contained smenamide A and B, along with smenamide C and two minor unidentified isomeric compounds at m/z 487.23 previously detected and described in reference [11]. Cluster 2 contained smenamide E and three more compounds, smenamides F ( 1 ) and G ( 2 ), and an unidentified analogue at m/z 533.28.…”

“…Cluster 2 contained smenamide E and three more compounds, smenamides F ( 1 ) and G ( 2 ), and an unidentified analogue at m/z 533.28. These nodes were also present in the network reported in [11], although they are not discussed in the text.…”

“…Recently, the family of smenamide compounds was further expanded with the isolation of smenamides C, D, and E. Interestingly, smenamides C ( 5 ) and E ( 7 ) showed moderate neurotoxicity against neuro-2A cells, while smenamide D ( 6 ), the geometric isomer of 5 , did not show any cytotoxic activity [10]. Moreover, it is interesting to cite a recent publication by Cantrell et al in which molecular networking in combination with MS2LDA analysis allowed to describe the intra and inter-chemical diversity present in a S. aurea sample collected in Florida Keys [11].…”

Metabolomics and Marine Biotechnology: Coupling Metabolite Profiling and Organism Biology for the Discovery of New Compounds

“…The development of high-throughput techniques such as genomics and metabolomics (i.e., the study of all small molecules, <2,000 Da, in an organism) promises to revolutionize natural product discovery, which according to some estimates, could outpace antibiotic discovery at its peak in the 1950s (Fortman and Mukhopadhyay, 2016). The use of these techniques, does not only offer an increase in the speed of natural product discovery and decrease in the rediscovery rate (Wolfender et al, 2019;van der Hooft et al, 2020), but provides a wide-array of unprecedented opportunities to discover unexplored chemical diversity and elucidate the biological and molecular mechanisms involved in metabolites production (e.g., Cantrell et al, 2019;Mohanty et al, 2020). Here, we provide a synthetic overview of the advantages of using metabolomic approaches in marine natural product discovery and marine biotechnology.…”