Ecology and genomics of Actinobacteria: new concepts for natural product discovery

• Published in: Nature reviews. Microbiology Vol. 18; no. 10; pp. 546 - 558
• Main Authors: van Bergeijk, Doris A., Terlouw, Barbara R., Medema, Marnix H., van Wezel, Gilles P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2020; Nature Publishing Group
• Subjects: 631/158/855; 631/326/22/1290; Actinobacteria; Actinobacteria - genetics; Actinobacteria - metabolism; Actinomycetes; Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antibiotics; Biological activity; Biological Products - isolation & purification; Biological Products - metabolism; Biological Products - pharmacology; Biomedical and Life Sciences; Computer applications; Drug Discovery; Ecology; Environmental aspects; Gene clusters; Gene Expression Regulation, Bacterial; Gene Transfer, Horizontal; Genes, Bacterial; Genetic aspects; Genome, Bacterial; Genomics; Genomics - methods; Humans; Infectious Diseases; Life Sciences; Medical Microbiology; Metabolic Networks and Pathways - genetics; Metabolism; Microbiology; Multigene Family; Natural products; Parasitology; Review Article; Streptomyces; Virology; Netherlands
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-020-0379-y

Actinobacteria constitute a highly diverse bacterial phylum with an unrivalled metabolic versatility. They produce most of the clinically used antibiotics and a plethora of other natural products with medical or agricultural applications. Modern ‘omics’-based technologies have revealed that the genomic potential of Actinobacteria greatly outmatches the known chemical space. In this Review, we argue that combining insights into actinobacterial ecology with state-of-the-art computational approaches holds great promise to unlock this unexplored reservoir of actinobacterial metabolism. This enables the identification of small molecules and other stimuli that elicit the induction of poorly expressed biosynthetic gene clusters, which should help reinvigorate screening efforts for their precious bioactive natural products. Actinobacteria are versatile producers of bioactive natural products. In this Review, van Wezel and colleagues discuss ecological and genomic insights into the mechanisms governing natural product metabolism and how those insights can be translated into approaches for computational and experimental genome mining strategies that yield novel bioactive molecules, in particular antibiotics.