When context matters: community and environmental context to elicit natural products

Natural products (NPs) comprise a wide range of bioactive compounds, including therapeutics and antibiotics. Despite several efforts, the discovery of novel NPs has been hindered by frequent rediscoveries of previously known NPs. Computational tools, such as those in genome mining, have helped identify the biosynthetic gene clusters (BGCs) responsible for the biosynthesis of NPs. However, there is a disconnect between the number of uncharacterized BGCs and the number of observed NPs in laboratory conditions. Considering the community and environmental context (C&EC) of NP-producing organisms can inform elicitation strategies to produce novel, uncharacterized NPs. Approaches inspired by nature, such as mimicking environmental conditions, introducing NPs as elicitors, and using multispecies co-cultures, have been proven successful in eliciting different responses in NP biosynthesis in the laboratory. However, the principles that drive how environmental conditions regulate NPs remain poorly understood. Integrating C&EC with genomic and metabolomic data enables the development of more rational, ecology-informed strategies for eliciting silent BGCs and discovering novel NPs.