Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi

ABSTRACT Filamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of the...

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Autores principales:	Jens Christian Nielsen, Sylvain Prigent, Sietske Grijseels, Mhairi Workman, Boyang Ji, Jens Nielsen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	comparative transcriptomics cell factories filamentous fungi secondary metabolism Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/769eda94cf9c460eb7770e7c395ae265
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spelling	oai:doaj.org-article:769eda94cf9c460eb7770e7c395ae2652021-12-02T19:46:17ZComparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi10.1128/mSystems.00012-192379-5077https://doaj.org/article/769eda94cf9c460eb7770e7c395ae2652019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00012-19https://doaj.org/toc/2379-5077ABSTRACT Filamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of the Penicillium genus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites. IMPORTANCE Secondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.Jens Christian NielsenSylvain PrigentSietske GrijseelsMhairi WorkmanBoyang JiJens NielsenAmerican Society for Microbiologyarticlecomparative transcriptomicscell factoriesfilamentous fungisecondary metabolismMicrobiologyQR1-502ENmSystems, Vol 4, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	comparative transcriptomics cell factories filamentous fungi secondary metabolism Microbiology QR1-502
spellingShingle	comparative transcriptomics cell factories filamentous fungi secondary metabolism Microbiology QR1-502 Jens Christian Nielsen Sylvain Prigent Sietske Grijseels Mhairi Workman Boyang Ji Jens Nielsen Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
description	ABSTRACT Filamentous fungi possess great potential as sources of medicinal bioactive compounds, such as antibiotics, but efficient production is hampered by a limited understanding of how their metabolism is regulated. We investigated the metabolism of six secondary metabolite-producing fungi of the Penicillium genus during nutrient depletion in the stationary phase of batch fermentations and assessed conserved metabolic responses across species using genome-wide transcriptional profiling. A coexpression analysis revealed that expression of biosynthetic genes correlates with expression of genes associated with pathways responsible for the generation of precursor metabolites for secondary metabolism. Our results highlight the main metabolic routes for the supply of precursors for secondary metabolism and suggest that the regulation of fungal metabolism is tailored to meet the demands for secondary metabolite production. These findings can aid in identifying fungal species that are optimized for the production of specific secondary metabolites and in designing metabolic engineering strategies to develop high-yielding fungal cell factories for production of secondary metabolites. IMPORTANCE Secondary metabolites are a major source of pharmaceuticals, especially antibiotics. However, the development of efficient processes of production of secondary metabolites has proved troublesome due to a limited understanding of the metabolic regulations governing secondary metabolism. By analyzing the conservation in gene expression across secondary metabolite-producing fungal species, we identified a metabolic signature that links primary and secondary metabolism and that demonstrates that fungal metabolism is tailored for the efficient production of secondary metabolites. The insight that we provide can be used to develop high-yielding fungal cell factories that are optimized for the production of specific secondary metabolites of pharmaceutical interest.
format	article
author	Jens Christian Nielsen Sylvain Prigent Sietske Grijseels Mhairi Workman Boyang Ji Jens Nielsen
author_facet	Jens Christian Nielsen Sylvain Prigent Sietske Grijseels Mhairi Workman Boyang Ji Jens Nielsen
author_sort	Jens Christian Nielsen
title	Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
title_short	Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
title_full	Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
title_fullStr	Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
title_full_unstemmed	Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
title_sort	comparative transcriptome analysis shows conserved metabolic regulation during production of secondary metabolites in filamentous fungi
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/769eda94cf9c460eb7770e7c395ae265
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Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi

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