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Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species
Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..ORCID iD: 0000-0002-6522-9987
Tech Univ Denmark, Dept Biotechnol & Biomed, DK-2800 Lyngby, Denmark..
Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..
Chalmers, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden..
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2017 (English)In: Nature Microbiology, ISSN 2058-5276, Vol. 2, no 6, 17044Article in journal (Refereed) Published
Abstract [en]

Filamentous fungi produce a wide range of bioactive compounds with important pharmaceutical applications, such as antibiotic penicillins and cholesterol-lowering statins. However, less attention has been paid to fungal secondary metabolites compared to those from bacteria. In this study, we sequenced the genomes of 9 Penicillium species and, together with 15 published genomes, we investigated the secondary metabolism of Penicillium and identified an immense, unexploited potential for producing secondary metabolites by this genus. A total of 1,317 putative biosynthetic gene clusters (BGCs) were identified, and polyketide synthase and non-ribosomal peptide synthetase based BGCs were grouped into gene cluster families and mapped to known pathways. The grouping of BGCs allowed us to study the evolutionary trajectory of pathways based on 6-methylsalicylic acid (6-MSA) synthases. Finally, we cross-referenced the predicted pathways with published data on the production of secondary metabolites and experimentally validated the production of antibiotic yanuthones in Penicillia and identified a previously undescribed compound from the yanuthone pathway. This study is the first genus-wide analysis of the genomic diversity of Penicillia and highlights the potential of these species as a source of new antibiotics and other pharmaceuticals.

Place, publisher, year, edition, pages
2017. Vol. 2, no 6, 17044
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-332214DOI: 10.1038/nmicrobiol.2017.44ISI: 000406000900009PubMedID: 28368369OAI: oai:DiVA.org:uu-332214DiVA: diva2:1152511
Funder
EU, FP7, Seventh Framework Programme, 607332Novo NordiskKnut and Alice Wallenberg FoundationSwedish National Infrastructure for Computing (SNIC)Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2017-10-27Bibliographically approved

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Dainat, Jacques

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Nielsen, Jens ChristianDainat, JacquesNielsen, Kristian FogNielsen, Jens
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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLab
Microbiology in the medical area

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