Control of Specialized Metabolism by Signaling and Transcriptional Regulation: Opportunities for New Platforms for Drug Discovery?

Specialized metabolites are bacterially produced small molecules that have an extraordinary diversity of important biological activities. They are useful as biochemical probes of living systems, and they have been adapted for use as drugs for human afflictions ranging from infectious diseases to cancer. The biosynthetic genes for these molecules are controlled by a dense network of regulatory mechanisms: Cell-cell signaling and nutrient sensing are conspicuous features of this network. While many components of these mechanisms have been identified, important questions about their biological roles remain shrouded in mystery. In addition to identifying new molecules and solving their mechanisms of action (a central preoccupation in this field), we suggest that addressing questions of quorum sensing versus diffusion sensing and identifying the dominant nutritional and environmental cues for specialized metabolism are important directions for research.