Journal article
Comparative Transcriptome Analysis Shows Conserved Metabolic Regulation during Production of Secondary Metabolites in Filamentous Fungi
Chalmers University of Technology1
Biosynthetic Pathway Engineering, Section for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark2
Department of Biotechnology and Biomedicine, Technical University of Denmark3
Fungal Physiology and Biotechnology, Department of Systems Biology, Technical University of Denmark4
Department of Systems Biology, Technical University of Denmark5
Bacterial Synthetic Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark6
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark7
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.
Language: | English |
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Publisher: | American Society for Microbiology |
Year: | 2019 |
Pages: | e00012-19-e00012-19 |
ISSN: | 23795077 |
Types: | Journal article |
DOI: | 10.1128/mSystems.00012-19 |
ORCIDs: | 0000-0002-6522-9987 and 0000-0002-9955-6003 |