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The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans
In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495134/ https://www.ncbi.nlm.nih.gov/pubmed/36139937 http://dx.doi.org/10.3390/antibiotics11091157 |
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author | Seghezzi, Nicolas Darbon, Emmanuelle Martel, Cécile David, Michelle Lejeune, Clara Esnault, Catherine Virolle, Marie-Joelle |
author_facet | Seghezzi, Nicolas Darbon, Emmanuelle Martel, Cécile David, Michelle Lejeune, Clara Esnault, Catherine Virolle, Marie-Joelle |
author_sort | Seghezzi, Nicolas |
collection | PubMed |
description | In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might be a direct trigger of antibiotic biosynthesis. In order to test this hypothesis, we introduced into the model strain Streptomyces lividans, a functional and a non-functional ATPase cloned into the replicative vector pOSV206 and expressed under the control of the strong ErmE* promoter. The functional ATPase was constituted by the α (AtpA), β (AtpB) and γ (AtpD) sub-units of the native F1 part of the ATP synthase of S. lividans that, when separated from the membrane-bound F0 part, bears an ATPase activity. The non-functional ATPase was a mutated version of the latter, bearing a 12 amino acids deletion encompassing the active site of the AtpD sub-unit. S. lividans was chosen to test our hypothesis since this strain hardly produces any antibiotics. However, it possesses the same biosynthetic pathways of various specialized metabolites as S. coelicolor, a phylogenetically closely related strain that produces these metabolites in abundance. Our results demonstrated that the over-expression of the functional ATPase, but not that of its mutated version, indeed correlated with the production of the bioactive metabolites of the CDA, RED and ACT clusters. These results confirmed the long known and mysterious link existing between a phosphate limitation leading to an ATP deficit and the triggering of antibiotic biosynthesis. Based on this work and the previous published results of our group, we propose an entirely novel conception of the nature of this link. |
format | Online Article Text |
id | pubmed-9495134 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94951342022-09-23 The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans Seghezzi, Nicolas Darbon, Emmanuelle Martel, Cécile David, Michelle Lejeune, Clara Esnault, Catherine Virolle, Marie-Joelle Antibiotics (Basel) Article In most Streptomyces species, antibiotic production is triggered in a condition of phosphate limitation, a condition that is known to be correlated with a low intracellular ATP content compared to growth in a condition of phosphate proficiency. This observation suggests that a low ATP content might be a direct trigger of antibiotic biosynthesis. In order to test this hypothesis, we introduced into the model strain Streptomyces lividans, a functional and a non-functional ATPase cloned into the replicative vector pOSV206 and expressed under the control of the strong ErmE* promoter. The functional ATPase was constituted by the α (AtpA), β (AtpB) and γ (AtpD) sub-units of the native F1 part of the ATP synthase of S. lividans that, when separated from the membrane-bound F0 part, bears an ATPase activity. The non-functional ATPase was a mutated version of the latter, bearing a 12 amino acids deletion encompassing the active site of the AtpD sub-unit. S. lividans was chosen to test our hypothesis since this strain hardly produces any antibiotics. However, it possesses the same biosynthetic pathways of various specialized metabolites as S. coelicolor, a phylogenetically closely related strain that produces these metabolites in abundance. Our results demonstrated that the over-expression of the functional ATPase, but not that of its mutated version, indeed correlated with the production of the bioactive metabolites of the CDA, RED and ACT clusters. These results confirmed the long known and mysterious link existing between a phosphate limitation leading to an ATP deficit and the triggering of antibiotic biosynthesis. Based on this work and the previous published results of our group, we propose an entirely novel conception of the nature of this link. MDPI 2022-08-27 /pmc/articles/PMC9495134/ /pubmed/36139937 http://dx.doi.org/10.3390/antibiotics11091157 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Seghezzi, Nicolas Darbon, Emmanuelle Martel, Cécile David, Michelle Lejeune, Clara Esnault, Catherine Virolle, Marie-Joelle The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title_full | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title_fullStr | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title_full_unstemmed | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title_short | The Generation of an Artificial ATP Deficit Triggers Antibiotic Production in Streptomyces lividans |
title_sort | generation of an artificial atp deficit triggers antibiotic production in streptomyces lividans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495134/ https://www.ncbi.nlm.nih.gov/pubmed/36139937 http://dx.doi.org/10.3390/antibiotics11091157 |
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