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

Abstract

The fungal genus of Aspergillus is 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 diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus, and A. steynii) have been whole-genome PacBio sequenced to provide genetic references in three Aspergillus sections. A. taichungensis and A. candidus also were sequenced for SM elucidation. Thirteen Aspergillus genomes 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. novofumigatus was compared with the pathogenic species A. fumigatus. This suggests that A. novofumigatus can produce most of the same allergens, virulence, and pathogenicity factors as A. fumigatus, suggesting that A. novofumigatus could be as pathogenic as A. fumigatus. Furthermore, 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 in A. ochraceoroseus, A. campestris, and A. steynii, respectively, and novofumigatonin, ent-cycloechinulin, and epi-aszonalenins in A. novofumigatus. Our study delivers six fungal genomes, showing the large diversitymore » found in the Aspergillus genus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports of A. novofumigatus pathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.« less

Authors:

Kjærbølling, Inge ^[1]; Vesth, Tammi C. ^[1]; Frisvad, Jens C. ^[1]; Nybo, Jane L. ^[1]; Theobald, Sebastian ^[1]; Kuo, Alan ^[2]; Bowyer, Paul ^[3]; Matsuda, Yudai ^[1]; Mondo, Stephen ^[2]; Lyhne, Ellen K. ^[1]; Kogle, Martin E. ^[1]; Clum, Alicia ^[2]; Lipzen, Anna ^[2]; Salamov, Asaf ^[2]; Ngan, Chew Yee ^[2]; Daum, Chris ^[2]; Chiniquy, Jennifer ^[2]; Barry, Kerrie ^[2]; LaButti, Kurt ^[2]; Haridas, Sajeet ^[2] more »; Simmons, Blake A.  ^[4];

• Search DOE PAGES for author "Simmons, Blake A."
• Search DOE PAGES for ORCID "0000-0002-1332-1810"

Magnuson, Jon K. ^[5]; Mortensen, Uffe H. ^[1]; Larsen, Thomas O. ^[1]; Grigoriev, Igor V. ^[6]; Baker, Scott E. ^[7]; Andersen, Mikael R.  ^[1]

• Search DOE PAGES for author "Andersen, Mikael R."
• Search DOE PAGES for ORCID "0000-0003-4794-6808"

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+ Show Author Affiliations

1. Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Lyngby, Denmark,
2. US Department of Energy Joint Genome Institute, Walnut Creek, CA 94598,
3. Manchester Fungal Infection Group, Institute of Inflammation and Repair, Faculty of Medicine and Human Sciences, University of Manchester, Manchester M13 9PL, United Kingdom,
4. US Department of Energy Joint BioEnergy Institute, Emeryville, CA 94608,, Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720,
5. US Department of Energy Joint BioEnergy Institute, Emeryville, CA 94608,, Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, WA 99352,
6. US Department of Energy Joint Genome Institute, Walnut Creek, CA 94598,, Plant and Microbial Biology Department, University of California Berkeley, Berkeley, CA 94720,
7. US Department of Energy Joint BioEnergy Institute, Emeryville, CA 94608,, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA 99352

Publication Date:

Tue Jan 09 00:00:00 EST 2018

Research Org.:

Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:

1416221

Alternate Identifier(s):

OSTI ID: 1439668; OSTI ID: 1465428

Report Number(s):

PNNL-SA-131168
Journal ID: ISSN 0027-8424

Grant/Contract Number:  

AC02-05CH11231; AC05-76RL01830

Resource Type:

Published Article

Journal Name:

Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:

Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 4; Journal ID: ISSN 0027-8424

Publisher:

Proceedings of the National Academy of Sciences

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; Aspergillus; fumigatus; comparative genomics; secondary metabolism