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

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Froslev Nielsen, Jens Christian,1987Chalmers tekniska högskola,Chalmers University of Technology (author)

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

Article/chapterEnglish2019

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2019
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LIBRIS-ID:oai:research.chalmers.se:e00dd0e0-e160-495b-bd9f-47978e4fe530
https://doi.org/10.1128/mSystems.00012-19DOI
https://research.chalmers.se/publication/512241URI
https://research.chalmers.se/publication/510393URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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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.

Subject headings and genre

NATURVETENSKAP Biologi Annan biologi hsv//swe
NATURAL SCIENCES Biological Sciences Other Biological Topics hsv//eng
NATURVETENSKAP Biologi Mikrobiologi hsv//swe
NATURAL SCIENCES Biological Sciences Microbiology hsv//eng
NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng
filamentous fungi
comparative transcriptomics
cell factories
secondary metabolism

Added entries (persons, corporate bodies, meetings, titles ...)

Prigent, Sylvain,1984Chalmers tekniska högskola,Chalmers University of Technology,Université de Bordeaux,University of Bordeaux(Swepub:cth)prigent (author)
Grijseels, SietskeDanmarks Tekniske Universitet,Technical University of Denmark (author)
Workman, MhairiDanmarks Tekniske Universitet,Technical University of Denmark (author)
Ji, Boyang,1983Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)bojand (author)
Nielsen, Jens B,1962Novo Nordisk Fonden,Novo Nordisk Foundation(Swepub:cth)nielsenj (author)
Chalmers tekniska högskolaUniversité de Bordeaux (creator_code:org_t)

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In:mSystems4:22379-5077

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Microbiology

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