The ubiquitous catechol moiety elicits siderophore and angucycline production in Streptomyces

Doris A Van Bergeijk,Chao Du,Somayah S Elsayed,Victor J Carrión,Isabel Nuñez Santiago,Herman P Spaink,Le Zhang,Gilles P Van Wezel,Anna M Roseboom

doi:10.1038/s42004-022-00632-4

Doris A Van Bergeijk, Chao Du + Show 7 more

Open Access

https://doi.org/10.1038/s42004-022-00632-4

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Abstract

Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored. However, many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. To exploit their full biosynthetic potential, better understanding of the signals that promote the expression of BGCs is needed. Here, we show that the human stress hormone epinephrine (adrenaline) elicits siderophore production by Actinobacteria. Catechol was established as the likely eliciting moiety, since similar responses were seen for catechol and for the catechol-containing molecules dopamine and catechin but not for related molecules. Exploration of the catechol-responsive strain Streptomyces sp. MBT84 using mass spectral networking revealed elicitation of a BGC that produces the angucycline glycosides aquayamycin, urdamycinone B and galtamycin C. Heterologous expression of the catechol-cleaving enzymes catechol 1,2-dioxygenase or catechol 2,3-dioxygenase counteracted the eliciting effect of catechol. Thus, our work identifies the ubiquitous catechol moiety as a novel elicitor of the expression of BGCs for specialized metabolites.

Highlights

Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored
We analyzed the effect of epinephrine, known as adrenaline, on a selection of our in-house actinobacterial strain collection that was previously shown to require particular growth conditions for the production of antibiotics[30]
To see if the addition of epinephrine to the growth media affected the susceptibility of the indicator strains against antibiotics, we added a diffusion disc with ampicillin (6 μg) to each plate and tested whether the presence of epinephrine in the growth medium affected the size of the inhibition zone of ampicillin against E. coli and B. subtilis

Summary

Introduction

Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored Many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. Next-generation sequencing technologies revealed a huge repository of previously unseen biosynthetic gene clusters (BGCs) in Actinobacteria, which showed that their potential as producers of bioactive molecules had been grossly underestimated[1,7,8] These BGCs are often not expressed under laboratory conditions, most likely because the environmental cues that activate their expression in their original habitat are missing[9,10]. These hormones are excreted by plants under pathogenic stress, and their release might represent a “cry for help” through which the plant may activate the production of bioactive substances by members of their microbiome, in order to counteract a pathogenic attack[24]

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