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July 19, 2019

Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species.

Authors: Kjærbølling, Inge and Vesth, Tammi C and Frisvad, Jens C and Nybo, Jane L and Theobald, Sebastian and Kuo, Alan and Bowyer, Paul and Matsuda, Yudai and Mondo, Stephen and Lyhne, Ellen K and Kogle, Martin E and Clum, Alicia and Lipzen, Anna and Salamov, Asaf and Ngan, Chew Yee and Daum, Chris and Chiniquy, Jennifer and Barry, Kerrie and LaButti, Kurt and Haridas, Sajeet and Simmons, Blake A and Magnuson, Jon K and Mortensen, Uffe H and Larsen, Thomas O and Grigoriev, Igor V and Baker, Scott E and Andersen, Mikael R

The fungal genus ofAspergillusis highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverseAspergillusspecies (A. campestris,A. novofumigatus,A. ochraceoroseus, andA. steynii) have been whole-genome PacBio sequenced to provide genetic references in threeAspergillussections.A. taichungensisandA. candidusalso were sequenced for SM elucidation. ThirteenAspergillusgenomes were analyzed with comparative genomics to determine phylogeny and genetic diversity, showing that each presented genome contains 15-27% genes not found in other sequenced Aspergilli. In particular,A. novofumigatuswas compared with the pathogenic speciesA. fumigatusThis suggests thatA. novofumigatuscan produce most of the same allergens, virulence, and pathogenicity factors asA. fumigatus, suggesting thatA. novofumigatuscould be as pathogenic asA. fumigatusFurthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences, and predictive algorithms. We thus identify putative SM clusters for aflatoxin, chlorflavonin, and ochrindol inA. ochraceoroseus,A. campestris, andA. steynii, respectively, and novofumigatonin,ent-cycloechinulin, andepi-aszonalenins inA. novofumigatusOur study delivers six fungal genomes, showing the large diversity found in theAspergillusgenus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports ofA. novofumigatuspathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.

Journal: Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1715954115
Year: 2018

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