oa Editorial [Hot Topic: Natural Products in Chemical Biology (Guest Editor: Jurg Gertsch)]

Secondary metabolism plays a major role in the evolution of organisms as they represent a source of highly diversified molecular scaffolds able to interact with multiple protein targets [1, 2]. Such interactions may both serve as molecular clues to deter competitors, or alternatively facilitate symbiosis [3, 4]. Thus, natural products are building blocks to generate and respond to evolutionary pressure. In the past millenia, humankind has relied on natural products for the elaboration of medicines and poisons [5, 6]. Indeed, some of the most influential molecules were discovered from medicinal and poisonous plants [7]. Insights into molecular mechanisms and the elucidation of macromolecular structures in the last fifty years has led to a targetbased approach in the discovery and design of novel drug leads. Despite the opportunities offered by fully synthetic libraries and biologics, natural products continue to play important roles as lead compounds and unique probes to manipulate biological systems. The still widely unexplored pools of secondary metabolites currently found in microorganisms, plants and animals in distinct ecological niches are highly dynamic and have most likely been selected for addressing a wide range of biological functions [8, 9]. This may be the reason why natural products have yielded a high number of molecules for drug development. The biosynthetic pathways leading to molecular diversity in microorganisms provide a new frontier for the rational generation of novel types of secondary metabolites. Moreover, a central aim of biological research is to elucidate the many roles of macromolecules in complex, dynamic living systems [10]. As uncovered in this issue, basic research directed against different organisms is revealing unexpected insights into fundamental biological roles of natural products and how these could be exploited in drug discovery. The review articles included in this hot topic issue of Current Drug Targets summarize current examples of how natural product diversity is being used in biological research and drug discovery, thus highlighting the natural products' outstanding properties and bioactivities from different perspectives. Overall, natural products are the prototype players in chemical biology. In the first review [11], Ramesha et al. provide an overview of the different approaches towards bioprospecting chemodiversity. The relationship between biological diversity and chemical diversity is discussed and non-random approaches in lead finding are indicated. In particular, chemical ecology-oriented algorithms are presented......