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


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.

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Fig. 1: From biological understanding to elicitation of BGCs.
Fig. 2: BGC distribution and evolution in Streptomyces chromosomes.
Fig. 3: Natural products of Actinobacteria in host–microorganism and microorganism–microorganism interactions.
Fig. 4: Omics strategies for BGC prioritization and elicitation.


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This work is supported by NACTAR grant 16440 from the Netherlands Organization for Scientific Research (NWO) to M.H.M. and G.P.v.W., and by the Profile area ‘Antibiotics’ of the Faculty of Sciences of Leiden University.

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The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Marnix H. Medema or Gilles P. van Wezel.

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Competing interests

M.H.M is a member of the Scientific Advisory Board of Hexagon Bio and co-founder of Design Pharmaceuticals. G.P.v.W. is in a committee for the Dutch Ministry of Health. D.A.v.B and B.R.T. do not declare any competing financial interests.

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Chelating specialized metabolites produced by bacteria and fungi, which form a soluble complex with iron and thereby facilitate the uptake of this essential element.


A dormant, non-reproductive structure that can survive for long periods of time and is important for dispersal of the organism in the environment.

Programmed cell death

(PCD). A cellular suicide mechanism found in eukaryotes and prokaryotes that is activated in response to different stimuli, including biotic and abiotic stresses.

Vegetative hyphae

Long filamentous cells with multiple chromosomes that grow by tip extension and branching, forming a dense network into the surrounding substrate (often referred to as the vegetative or substrate mycelium).

Sporogenic aerial hyphae

Reproductive hyphal structures that emerge from the vegetative mycelium into the air and develop into chains of unigenomic spores.

Saprophytic bacteria

Bacteria, often found in the soil, that feed on dead and decaying organic material.


A family of red-pigmented, bacterial, specialized metabolites with a wide range of biological activities, including antibacterial, antitumour and immunosuppressive properties.


A blue-pigmented polyketide antibiotic that is a model for polyketide biosynthesis.


Bacterial specialized metabolites that act as osmolytes and protect against osmotic stress induced by, for example, changes in salt concentration of the environment.


A class of specialized metabolites produced by plants, fungi and bacteria with different biological activities, often volatile and with a strong odour.


The region of the soil and its microbial community immediately surrounding the plant root, which is directly influenced by root exudates.

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van Bergeijk, D.A., Terlouw, B.R., Medema, M.H. et al. Ecology and genomics of Actinobacteria: new concepts for natural product discovery. Nat Rev Microbiol 18, 546–558 (2020).

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