ERA-NET: Prostist Metabolome Screening

Marine single-celled eukaryotes, called protists, have a large but underexploited reservoir of metabolic synthesis pathways and metabolites (biochemical compounds) with a biotechnological potential. Through evolution, protists have developed complex cells with properties, metabolites, metabolic synthesis pathways, and bioactivities different from those of bacteria. There are therefore great opportunities to discover different bioactivities compared to those previously identified in bacteria. In the PROMISE project, we use a range of various genomic analyses (omics methods) such as metabarcoding, genomics, transcriptomics and metabolomics of protists from the sea. These methods tell us which protists are present in the samples, all the genes they have, which genes are expressed and which compounds they produce. The goal is to identify candidate compounds and their related metabolites and infer their bioactivity. In the PROMISE project, we also perform single-cell genomic analyses in protist cells isolated directly from marine samples and can thus recognise functional gene clusters and better understand how metabolic pathways occur in natural marine protist communities, how identified metabolic pathways function in nature and how they can be expressed and utilised for technological innovation that is relevant in medicine and biotechnology. The integrated assay procedure is supported by a range of biological tests to verify bioactivities by mass profiling and antibacterial activity screening. Analytical chemistry, including high-resolution mass spectroscopy and atomic magnetic resonance spectroscopy are used to elucidate the structure of compounds found in the bioactive fractions. This is linking molecular biological data to identified, relevant enzymes and other compounds, as well as their metabolism.

A major significance for society from the project is the documentation and in-depth analyses of the toxic algal bloom in 2019 killing 14500 tonnes of farmed fish in Northern Norway, which have and will give a better understanding of the causes for the bloom formation and its toxicity, and the toxins involved. This may enable the fish farmers to reduce the risk of fish loss in the future. Our work will also improve our understanding of the evolution in this important algal group and elucidate differences in metabolic pathways. This project has demonstrated the value of integrating various -omics methods and research disciplines (marine ecology, chemistry, molecular biology) to better understand what type of compounds a protist can produce and their bioactivity.

Marine eukaryotic protists offer a huge but currently underexploited reservoir of metabolic pathways with biotechnological potential. Given their unique adaptations through symbiosis, endosymbiosis and organelle acquisition, the ecofunctionalities of protists present a hitherto untapped source to discover novel metabolic pathways and bioactivities whilst bearing a high chance of discovering different activities compared to those identified in e.g. marine bacteria. The scientific approach and rationale sets PROMiSE apart from previous scientific initiatives exploiting the biotechnological potential of marine bacteria. The PROMiSE experimental workflow enables this by employing a comprehensive set of Omics methods. This approach spans the encoded metabolic potential to identify biosynthetic gene clusters which in turn guide the targeted metabolite profiling, merged with discovery-based metabolomics. The goal is to target identified candidate compound classes and their pathway-related metabolites and conjugations dereplicated from the Omics information. By linking these methods back to the source cell through single cell Omic methods, PROMiSE offers a unique way to recognize functional gene clusters and to understand how metabolism is partitioned across ecosystems. We will unravel how identified pathways work in nature and how they can be expressed and utilized for technological adaptations relevant to a human health and biotechnology market. The vertically integrated extraction and analyses procedure are supported by a comprehensive array of cutting-edge in vitro and in vivo bioassays for reliably assessing biological activities by high-content profiling and antibacterial screening. Analytical chemistry, including high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy approaches, will be used to elucidate compounds found in the bioactive fractions, which will tie back the molecular data to identify relevant enzymes, pathways, and compounds.