Marine microbial eukaryotes offer a huge but currently underexploited reservoir of metabolic pathways with biotechnological potential. Indeed, some of the greatest discoveries of bioactive compounds have been derived from eukaryotes, a historic example being Flemings discovery of antibiotics in fungi. While prokaryotes (bacteria and archaea) are numerically dominant in all marine habitats and perform unique and increasingly well understood metabolic processes, the protists - a phylogenetically broad group of eukaryotic microbes living as single cells or colonies that exhibit coordinated behaviour - are also important ecological players in the ocean. In addition to the myriad of predatorprey relationships, the interactions of protists with other microorganisms and multicellular organisms have brought forward a wide range of mutual associations including competition, parasitism, commensalism and mutualism. These associational adaptations are hypothesized to result in enzymatically, metabolically and mechanistically unique and effective strategies, notably different from those of bacteria, to cope with environmental challenges and threats. The main scientific objective of the project PROMiSE is to screen natural protist assemblages for detecting novel discoveries of biotechnological significance. As microbial eukaryotes have been grossly understudied in comparison with macroscopic eukaryotes or non-eukaryotic microbes, they represent an enormous reservoir of untapped metabolic and biotechnological potential, just as bacteria did two decades ago. Given the unique adaptations of protists through symbiosis, endosymbiosis and organelle acquisition, their functionalities under natural conditions present a hitherto untapped source to discover novel metabolic pathways and bioactivities. This scientific approach and rationale sets PROMiSE apart from the many previous scientific initiatives exploiting the biotechnological potential of marine bacteria. The experimental workflow of PROMiSE will enable this challenging goal by employing a comprehensive set of Omics methods, from encoded genetic potential, to gene expression and produced metabolites. Discovery-based metabolomics will be employed to target known compound classes, and their pathway-related metabolites and conjugations will be dereplicated from the Omics information in biosynthetic gene clusters. By linking these methods back to the biological source cell through single cell Omics methods, PROMiSE offers a unique way to recognize functional gene clusters and how metabolism is partitioned across populations and communities, which will play an increasingly important role in understanding how complex metabolic pathways work in nature and by extension how they can be expressed and utilized for biotechnological adaptations. With its focus on some of the least- investigated corners of biology using state of the art techniques never applied to these systems, PROMiSE bears high innovative potential to discover novel pathways and compound classes with the potential to address medical needs of current concern, such as polyketides and quorum quenching signals as well as novel antibiotics.