A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators

ABSTRACT Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity....

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Autores principales:	Loïc Martinet, Aymeric Naômé, Benoit Deflandre, Marta Maciejewska, Déborah Tellatin, Elodie Tenconi, Nicolas Smargiasso, Edwin de Pauw, Gilles P. van Wezel, Sébastien Rigali
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Streptomyces genome analysis iron regulation natural antimicrobial products secondary metabolism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/487c5b0fc4fa487a83ca337229a10141
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spelling	oai:doaj.org-article:487c5b0fc4fa487a83ca337229a101412021-11-15T16:22:11ZA Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators10.1128/mBio.01230-192150-7511https://doaj.org/article/487c5b0fc4fa487a83ca337229a101412019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01230-19https://doaj.org/toc/2150-7511ABSTRACT Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, representing amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus, our work shows a unique exception to the concept that BGCs should only produce a single family of molecules with one type of bioactivity and that in fact different bioactive molecules may be produced depending on the environmental conditions. IMPORTANCE Access to whole-genome sequences has exposed the general incidence of the so-called cryptic biosynthetic gene clusters (BGCs), thereby renewing their interest for natural product discovery. As a consequence, genome mining is the often first approach implemented to assess the potential of a microorganism for producing novel bioactive metabolites. By revealing a new level of complexity of natural product biosynthesis, we further illustrate the difficulty of estimation of the panel of molecules associated with a BGC based on genomic information alone. Indeed, we found that the same gene cluster is responsible for the production of compounds which differ in terms of structure and bioactivity. The production of these different compounds responds to different environmental triggers, which suggests that multiplication of culture conditions is essential for revealing the entire panel of molecules made by a single BGC.Loïc MartinetAymeric NaôméBenoit DeflandreMarta MaciejewskaDéborah TellatinElodie TenconiNicolas SmargiassoEdwin de PauwGilles P. van WezelSébastien RigaliAmerican Society for MicrobiologyarticleStreptomycesgenome analysisiron regulationnatural antimicrobial productssecondary metabolismMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptomyces genome analysis iron regulation natural antimicrobial products secondary metabolism Microbiology QR1-502
spellingShingle	Streptomyces genome analysis iron regulation natural antimicrobial products secondary metabolism Microbiology QR1-502 Loïc Martinet Aymeric Naômé Benoit Deflandre Marta Maciejewska Déborah Tellatin Elodie Tenconi Nicolas Smargiasso Edwin de Pauw Gilles P. van Wezel Sébastien Rigali A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
description	ABSTRACT Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, representing amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus, our work shows a unique exception to the concept that BGCs should only produce a single family of molecules with one type of bioactivity and that in fact different bioactive molecules may be produced depending on the environmental conditions. IMPORTANCE Access to whole-genome sequences has exposed the general incidence of the so-called cryptic biosynthetic gene clusters (BGCs), thereby renewing their interest for natural product discovery. As a consequence, genome mining is the often first approach implemented to assess the potential of a microorganism for producing novel bioactive metabolites. By revealing a new level of complexity of natural product biosynthesis, we further illustrate the difficulty of estimation of the panel of molecules associated with a BGC based on genomic information alone. Indeed, we found that the same gene cluster is responsible for the production of compounds which differ in terms of structure and bioactivity. The production of these different compounds responds to different environmental triggers, which suggests that multiplication of culture conditions is essential for revealing the entire panel of molecules made by a single BGC.
format	article
author	Loïc Martinet Aymeric Naômé Benoit Deflandre Marta Maciejewska Déborah Tellatin Elodie Tenconi Nicolas Smargiasso Edwin de Pauw Gilles P. van Wezel Sébastien Rigali
author_facet	Loïc Martinet Aymeric Naômé Benoit Deflandre Marta Maciejewska Déborah Tellatin Elodie Tenconi Nicolas Smargiasso Edwin de Pauw Gilles P. van Wezel Sébastien Rigali
author_sort	Loïc Martinet
title	A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
title_short	A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
title_full	A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
title_fullStr	A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
title_full_unstemmed	A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators
title_sort	single biosynthetic gene cluster is responsible for the production of bagremycin antibiotics and ferroverdin iron chelators
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/487c5b0fc4fa487a83ca337229a10141
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A Single Biosynthetic Gene Cluster Is Responsible for the Production of Bagremycin Antibiotics and Ferroverdin Iron Chelators

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