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The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum

The filamentous fungus Acremonium chrysogenum is the main industrial producer of cephalosporin C (CPC), one of the major precursors for manufacturing of cephalosporin antibiotics. The plasma membrane H(+)-ATPase (PMA) plays a key role in numerous fungal physiological processes. Previously we observe...

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Autores principales: Zhgun, Alexander, Dumina, Mariya, Valiakhmetov, Ayrat, Eldarov, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458343/
https://www.ncbi.nlm.nih.gov/pubmed/32866191
http://dx.doi.org/10.1371/journal.pone.0238452
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author Zhgun, Alexander
Dumina, Mariya
Valiakhmetov, Ayrat
Eldarov, Mikhail
author_facet Zhgun, Alexander
Dumina, Mariya
Valiakhmetov, Ayrat
Eldarov, Mikhail
author_sort Zhgun, Alexander
collection PubMed
description The filamentous fungus Acremonium chrysogenum is the main industrial producer of cephalosporin C (CPC), one of the major precursors for manufacturing of cephalosporin antibiotics. The plasma membrane H(+)-ATPase (PMA) plays a key role in numerous fungal physiological processes. Previously we observed a decrease of PMA activity in A. chrysogenum overproducing strain RNCM 408D (HY) as compared to the level the wild-type strain A. chrysogenum ATCC 11550. Here we report the relationship between PMA activity and CPC biosynthesis in A. chrysogenum strains. The elevation of PMA activity in HY strain through overexpression of PMA1 from Saccharomyces cerevisiae, under the control of the constitutive gpdA promoter from Aspergillus nidulans, results in a 1.2 to 10-fold decrease in CPC production, shift in beta-lactam intermediates content, and is accompanied by the decrease in cef genes expression in the fermentation process; the characteristic colony morphology on agar media is also changed. The level of PMA activity in A. chrysogenum HY OE::PMA1 strains has been increased by 50–100%, up to the level observed in WT strain, and was interrelated with ATP consumption; the more PMA activity is elevated, the more ATP level is depleted. The reduced PMA activity in A. chrysogenum HY strain may be one of the selected events during classical strain improvement, aimed at elevating the ATP content available for CPC production.
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spelling pubmed-74583432020-09-04 The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum Zhgun, Alexander Dumina, Mariya Valiakhmetov, Ayrat Eldarov, Mikhail PLoS One Research Article The filamentous fungus Acremonium chrysogenum is the main industrial producer of cephalosporin C (CPC), one of the major precursors for manufacturing of cephalosporin antibiotics. The plasma membrane H(+)-ATPase (PMA) plays a key role in numerous fungal physiological processes. Previously we observed a decrease of PMA activity in A. chrysogenum overproducing strain RNCM 408D (HY) as compared to the level the wild-type strain A. chrysogenum ATCC 11550. Here we report the relationship between PMA activity and CPC biosynthesis in A. chrysogenum strains. The elevation of PMA activity in HY strain through overexpression of PMA1 from Saccharomyces cerevisiae, under the control of the constitutive gpdA promoter from Aspergillus nidulans, results in a 1.2 to 10-fold decrease in CPC production, shift in beta-lactam intermediates content, and is accompanied by the decrease in cef genes expression in the fermentation process; the characteristic colony morphology on agar media is also changed. The level of PMA activity in A. chrysogenum HY OE::PMA1 strains has been increased by 50–100%, up to the level observed in WT strain, and was interrelated with ATP consumption; the more PMA activity is elevated, the more ATP level is depleted. The reduced PMA activity in A. chrysogenum HY strain may be one of the selected events during classical strain improvement, aimed at elevating the ATP content available for CPC production. Public Library of Science 2020-08-31 /pmc/articles/PMC7458343/ /pubmed/32866191 http://dx.doi.org/10.1371/journal.pone.0238452 Text en © 2020 Zhgun et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhgun, Alexander
Dumina, Mariya
Valiakhmetov, Ayrat
Eldarov, Mikhail
The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title_full The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title_fullStr The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title_full_unstemmed The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title_short The critical role of plasma membrane H(+)-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum
title_sort critical role of plasma membrane h(+)-atpase activity in cephalosporin c biosynthesis of acremonium chrysogenum
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458343/
https://www.ncbi.nlm.nih.gov/pubmed/32866191
http://dx.doi.org/10.1371/journal.pone.0238452
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