Prospecting aquatic and terrestrial natural biological resources for biologically active compounds Proposals should cover the entire development pipeline with a focus on:biodiscovery (prospecting natural biological resources from land and sea), i.e.: identifying suitable molecules;verifying their claimed benefits;optimising technological exploitation, including cultivation strategies for selected production systems and metabolic engineering to ensure high productivity and purity;assessing safety, anddeveloping products (final formulation) and their commercialisation, in Europe. Proposals should focus on small molecules[[Defined as chemical compounds or substances that are produced naturally by living organisms, such as bioactive secondary metabolites (e.g. alkaloids, terpenoids, flavonoids, glycosides, polyketides and peptides), and/or their derivatives. Large macromolecules such as proteins/enzymes are excluded.]], with novel bioactivities, qualities and applications, in particular from unusual or underutilised sources, and on our understanding of their relevant chemical, genetic, physiological and environmental make-up. Special attention should be devoted to ensuring sustainable sourcing from the raw feedstock, to avoid overexploitation, taking into account recent technical advances in molecular biology (e.g. metabolomics, new gene mining and optimisation techniques, development of suitable host production platforms). Proposals could explore in vivo or in vitro approaches to study the interactions between various biological entities (e.g. through symbiotic or defence relationships) as a source of interesting bioactive properties. They should:prove the techno-economic feasibility and effectiveness of a chosen production route[[Including, if appropriate, an outline of continuation of the end-product development beyond the project timeline and its resources.]];commit to assessing, as part of the project, the environmental and health impacts of the developed products or processes, using life-cycle assessment (LCA) methodologies based on available standards, certification, and accepted and validated approaches, andguarantee biodiversity preservation and comply with relevant international rules on access to biological resources, their sustainable use and the fair and equitable sharing of benefits from their utilisation, with the national regulations in the source countries and with the Convention on Biological Diversity and its Nagoya Protocol. In line with the EU’s policy on responsible research and innovation, dissemination and public engagement via modern communication and dissemination tools will be an essential element of the projects that are funded. Projects should involve an analysis of the state of the art to avoid duplications and overlaps with past or ongoing research. Cooperation with other selected proposals under this topic is encouraged.Proposals should address one of the following sub-topics:A: Prospecting terrestrial natural biological resources for biologically active compoundsActions must focus on land-based biological natural resources.B: Prospecting aquatic natural biological resources for biologically active compoundsActions must focus on marine and fresh-water biological natural resources.The Commission considers that proposals requesting an EU contribution of around EUR 7.5 million would allow this specific challenge to be addressed appropriately. This does not preclude the submission and selection of proposals requesting other amounts. Global biodiversity remains a largely untapped source of natural bioactive molecules and compounds. Such molecules offer unmatched chemical diversity and structural complexity, together with biological potency and selectivity. While some of the natural chemodiversity has been studied, resulting in open access and proprietary compound libraries, the potential for developing commercial products is far from exhausted. There is still significant potential for application in various industries, such as high-value agro-chemicals (e.g. natural plant protection products), food and feed ingredients (such as nutraceuticals), pharmaceutically active ingredients, cosmetics, flavourings etc. On conservative estimates, these compounds represent a global market of EUR 150 billion[[“The role of biomass and bioenergy in a future bioeconomy: policies and facts” (2015) World Markets 2012 European Commission, Joint Research Centre (JRC).]] and global industrial revenues of EUR 19 billion[[Frost and Sullivan revenues by end-user industry (2010 world) Fraunhofer White Biotechnology, N8E3-39 (June 2011).]].The main challenges tackled in the topic are, depending on the source:technological readiness for the sustainable exploitation of natural resources, linked with;scarcity of the source natural biological material (e.g. in case of protected / rare species);low concentrations of the target compounds, leading to the difficulties in obtaining sufficient amounts of the pure molecules. The challenge is to match their sustainable sourcing and processing with efficient and cost-effective use. This calls for close cooperation between industrial and academic partners, with due consideration for health and environmental legislation, and informed public engagement. Activities will support the sustainable biodiscovery and use of natural biological resources from diverse environments and ecosystems, allowing better assessment of the selected bioactivity potential. This will increase capacity in the European biotechnology sector and other industries to respond to society’s needs. Specifically, activities will contribute to:Short/medium term:developing novel natural, sustainable and ‘eco-friendly’ products with significant bioactive properties, especially as relevant for the pharmaceutical, cosmetic, agrochemical or marine sectors and applications. These will deliver clear-cut benefits for consumers by being more effective and/or eco-friendly, cheaper, and more readily accessible than existing alternatives;developing sustainable exploitation, cultivation and processing methods based on promising species/organisms, and chosen production routes;increasing public-private cooperation in European biotechnology, while integrating its sectors e.g. ‘green’ (plant), ‘blue’ (marine), and ‘white’ (industrial); and;increasing public knowledge of biodiversity potential and, if relevant, ecosystem interactions, and their impact on bioactive response; Long term:reducing the pressure on the harvesting of wild populations; and;ensuring the environmental and economic sustainability of the entire process, inter alia by reducing and extracting waste via the efficient use of biomass (cascade approach).