title: Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species.
abstract: 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.
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.
authors.forename: Jens Christian
authors.identifier: http://orcid.org/0000-0002-6522-9987
authors.initials: JC
authors.lastname: Nielsen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, DK2800 Kgs. Lyngby, Denmark.
authors.forename: Sietske
authors.initials: S
authors.lastname: Grijseels
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Prigent
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.
authors.forename: Boyang
authors.initials: B
authors.lastname: Ji
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.|National Bioinformatics Infrastructure Sweden (NBIS), SciLifeLab, Uppsala University, 752 37 Uppsala, Sweden.
authors.forename: Jacques
authors.initials: J
authors.lastname: Dainat
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, DK2800 Kgs. Lyngby, Denmark.
authors.forename: Kristian Fog
authors.initials: KF
authors.lastname: Nielsen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, DK2800 Kgs. Lyngby, Denmark.
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Frisvad
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, DK2800 Kgs. Lyngby, Denmark.
authors.forename: Mhairi
authors.initials: M
authors.lastname: Workman
authors.affiliation: Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK2800 Kgs. Lyngby, Denmark.
authors.forename: Jens
authors.identifier: http://orcid.org/0000-0002-6522-9987
authors.initials: J
authors.lastname: Nielsen
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D053898:Biosynthetic Pathways / Q000235:genetics*; D005658:Fungi / Q000235:genetics; D020869:Gene Expression Profiling; D014644:Genetic Variation; D016681:Genome, Fungal; D023281:Genomics; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010407:Penicillium / Q000235:genetics* / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D048630:Polyketide Synthases / Q000235:genetics; D064210:Secondary Metabolism / Q000235:genetics*; D013729:Terpenes / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D009097:Multienzyme Complexes; D013729:Terpenes; C000595675:yanuthone D; D048630:Polyketide Synthases; D010088:Oxidoreductases; D000217:Acyltransferases; C021587:6-methylsalicylic acid synthetase; D008025:Ligases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase