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Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism?
In recent years, genome sequencing of filamentous fungi has revealed a high proportion of specialised metabolites with growing pharmaceutical interest. However, detecting such metabolites through in silico genome analysis does not necessarily guarantee their expression under laboratory conditions. H...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468094/ https://www.ncbi.nlm.nih.gov/pubmed/37647283 http://dx.doi.org/10.1371/journal.pone.0289757 |
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author | Nègre, Delphine Larhlimi, Abdelhalim Bertrand, Samuel |
author_facet | Nègre, Delphine Larhlimi, Abdelhalim Bertrand, Samuel |
author_sort | Nègre, Delphine |
collection | PubMed |
description | In recent years, genome sequencing of filamentous fungi has revealed a high proportion of specialised metabolites with growing pharmaceutical interest. However, detecting such metabolites through in silico genome analysis does not necessarily guarantee their expression under laboratory conditions. However, one plausible strategy for enabling their production lies in modifying the growth conditions. Devising a comprehensive experimental design testing in different culture environments is time-consuming and expensive. Therefore, using in silico modelling as a preliminary step, such as Genome-Scale Metabolic Network (GSMN), represents a promising approach to predicting and understanding the observed specialised metabolite production in a given organism. To address these questions, we reconstructed a new high-quality GSMN for the Penicillium rubens Wisconsin 54–1255 strain, a commonly used model organism. Our reconstruction, iPrub22, adheres to current convention standards and quality criteria, incorporating updated functional annotations, orthology searches with different GSMN templates, data from previous reconstructions, and manual curation steps targeting primary and specialised metabolites. With a MEMOTE score of 74% and a metabolic coverage of 45%, iPrub22 includes 5,192 unique metabolites interconnected by 5,919 reactions, of which 5,033 are supported by at least one genomic sequence. Of the metabolites present in iPrub22, 13% are categorised as belonging to specialised metabolism. While our high-quality GSMN provides a valuable resource for investigating known phenotypes expressed in P. rubens, our analysis identifies bottlenecks related, in particular, to the definition of what is a specialised metabolite, which requires consensus within the scientific community. It also points out the necessity of accessible, standardised and exhaustive databases of specialised metabolites. These questions must be addressed to fully unlock the potential of natural product production in P. rubens and other filamentous fungi. Our work represents a foundational step towards the objective of rationalising the production of natural products through GSMN modelling. |
format | Online Article Text |
id | pubmed-10468094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104680942023-08-31 Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? Nègre, Delphine Larhlimi, Abdelhalim Bertrand, Samuel PLoS One Research Article In recent years, genome sequencing of filamentous fungi has revealed a high proportion of specialised metabolites with growing pharmaceutical interest. However, detecting such metabolites through in silico genome analysis does not necessarily guarantee their expression under laboratory conditions. However, one plausible strategy for enabling their production lies in modifying the growth conditions. Devising a comprehensive experimental design testing in different culture environments is time-consuming and expensive. Therefore, using in silico modelling as a preliminary step, such as Genome-Scale Metabolic Network (GSMN), represents a promising approach to predicting and understanding the observed specialised metabolite production in a given organism. To address these questions, we reconstructed a new high-quality GSMN for the Penicillium rubens Wisconsin 54–1255 strain, a commonly used model organism. Our reconstruction, iPrub22, adheres to current convention standards and quality criteria, incorporating updated functional annotations, orthology searches with different GSMN templates, data from previous reconstructions, and manual curation steps targeting primary and specialised metabolites. With a MEMOTE score of 74% and a metabolic coverage of 45%, iPrub22 includes 5,192 unique metabolites interconnected by 5,919 reactions, of which 5,033 are supported by at least one genomic sequence. Of the metabolites present in iPrub22, 13% are categorised as belonging to specialised metabolism. While our high-quality GSMN provides a valuable resource for investigating known phenotypes expressed in P. rubens, our analysis identifies bottlenecks related, in particular, to the definition of what is a specialised metabolite, which requires consensus within the scientific community. It also points out the necessity of accessible, standardised and exhaustive databases of specialised metabolites. These questions must be addressed to fully unlock the potential of natural product production in P. rubens and other filamentous fungi. Our work represents a foundational step towards the objective of rationalising the production of natural products through GSMN modelling. Public Library of Science 2023-08-30 /pmc/articles/PMC10468094/ /pubmed/37647283 http://dx.doi.org/10.1371/journal.pone.0289757 Text en © 2023 Nègre et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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 Nègre, Delphine Larhlimi, Abdelhalim Bertrand, Samuel Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title | Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title_full | Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title_fullStr | Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title_full_unstemmed | Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title_short | Reconciliation and evolution of Penicillium rubens genome-scale metabolic networks–What about specialised metabolism? |
title_sort | reconciliation and evolution of penicillium rubens genome-scale metabolic networks–what about specialised metabolism? |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468094/ https://www.ncbi.nlm.nih.gov/pubmed/37647283 http://dx.doi.org/10.1371/journal.pone.0289757 |
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