Abstract
The high diversity of marine natural products represents promising opportunities for drug discovery, an important area in marine biotechnology. Within this context, high-throughput techniques such as metabolomics are extremely useful in unveiling unexplored chemical diversity at much faster rates than classical bioassay-guided approaches. Metabolomics approaches enable studying large sets of metabolites, even if they are produced at low concentrations. Although, metabolite identification remains the main metabolomics bottleneck, bioinformatic tools such as molecular networks can lead to the annotation of unknown metabolites and discovery of new compounds. A metabolomic approach in drug discovery has two major advantages: it enables analyses of multiple samples, allowing fast dereplication of already known compounds and provides a unique opportunity to relate metabolite profiles to organisms’ biology. Understanding the ecological and biological factors behind a certain metabolite production can be extremely useful in enhancing compound yields, optimizing compound extraction or in selecting bioactive compounds. Metazoan-associated microbiota are often responsible for metabolite synthesis, however, classical approaches only allow studying metabolites produced from cultivatable microbiota, which often differ from the compounds produced within the host. Therefore, coupling holobiome metabolomics with microbiome analysis can bring new insights to the role of microbiota in compound production. The ultimate potential of metabolomics is its coupling with other “omics” (i.e., transcriptomics and metagenomics). Although, such approaches are still challenging, especially in non-model species where genomes have not been annotated, this innovative approach is extremely valuable in elucidating gene clusters associated with biosynthetic pathways and will certainly become increasingly important in marine drug discovery.
Highlights
Natural products are key to drug development, and have proved especially useful in the development of anticancer and anti-infective agents (Rodrigues et al, 2016; Liu et al, 2019)
Marine organisms arise as a prolific source of novel natural products, with an economic value estimated at US$ 563 billion – 5.7 trillion for only anticancer marine drugs (Erwinn et al, 2010; Abdelmohsen et al, 2017)
The production of highly bioactive organohalogens seems to be widespread amongst marine organisms, but is less common amongst terrestrial organisms (Gribble, 2010)
Summary
Natural products (i.e., compounds produced by living organisms) are key to drug development, and have proved especially useful in the development of anticancer and anti-infective agents (Rodrigues et al, 2016; Liu et al, 2019). The marine environment, which harbors a large and yet highly unexplored biodiversity, is an extremely rich source of novel and structurally unique compounds with antibacterial, antifungal, antiviral, antiparasitic, antitumor, anti-inflammatory, antioxidant and immunomodulatory activities (Abdelmohsen et al, 2017; Carroll et al, 2020; Mayer et al, 2020) Some marine organisms such as sponges are amongst the most prolific sources of natural products, suggesting that the marine environment is a reservoir of natural products with high relevance for marine biotechnology and drug discovery (including against resistant pathogens) (Thakur and Müller, 2004, Abdelmohsen et al, 2017; Liu et al, 2019). Metabolomics is a scientific field at the interface of different disciplines (chemistry, bioinformatics, ecology, microbiology, and systems biology); this mini-review aims to illustrate how the multidisciplinarity of metabolomics is a key asset for the advancement of marine natural product discovery
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