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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 -aszonaleninsmore » in A. novofumigatus . Our study delivers six fungal genomes, showing the large diversity 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:
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Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1416221
Alternate Identifier(s):
OSTI ID: 1439668; OSTI ID: 1465428
Report Number(s):
PNNL-SA-131168
Journal ID: ISSN 0027-8424; /pnas/115/4/E753.atom
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

Citation Formats

Kjærbølling, Inge, Vesth, Tammi C., Frisvad, Jens C., Nybo, Jane L., Theobald, Sebastian, Kuo, Alan, Bowyer, Paul, Matsuda, Yudai, Mondo, Stephen, Lyhne, Ellen K., Kogle, Martin E., Clum, Alicia, Lipzen, Anna, Salamov, Asaf, Ngan, Chew Yee, Daum, Chris, Chiniquy, Jennifer, Barry, Kerrie, LaButti, Kurt, Haridas, Sajeet, Simmons, Blake A., Magnuson, Jon K., Mortensen, Uffe H., Larsen, Thomas O., Grigoriev, Igor V., Baker, Scott E., and Andersen, Mikael R. Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species. United States: N. p., 2018. Web. doi:10.1073/pnas.1715954115.
Kjærbølling, Inge, Vesth, Tammi C., Frisvad, Jens C., Nybo, Jane L., Theobald, Sebastian, Kuo, Alan, Bowyer, Paul, Matsuda, Yudai, Mondo, Stephen, Lyhne, Ellen K., Kogle, Martin E., Clum, Alicia, Lipzen, Anna, Salamov, Asaf, Ngan, Chew Yee, Daum, Chris, Chiniquy, Jennifer, Barry, Kerrie, LaButti, Kurt, Haridas, Sajeet, Simmons, Blake A., Magnuson, Jon K., Mortensen, Uffe H., Larsen, Thomas O., Grigoriev, Igor V., Baker, Scott E., & Andersen, Mikael R. Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species. United States. doi:10.1073/pnas.1715954115.
Kjærbølling, Inge, Vesth, Tammi C., Frisvad, Jens C., Nybo, Jane L., Theobald, Sebastian, Kuo, Alan, Bowyer, Paul, Matsuda, Yudai, Mondo, Stephen, Lyhne, Ellen K., Kogle, Martin E., Clum, Alicia, Lipzen, Anna, Salamov, Asaf, Ngan, Chew Yee, Daum, Chris, Chiniquy, Jennifer, Barry, Kerrie, LaButti, Kurt, Haridas, Sajeet, Simmons, Blake A., Magnuson, Jon K., Mortensen, Uffe H., Larsen, Thomas O., Grigoriev, Igor V., Baker, Scott E., and Andersen, Mikael R. Tue . "Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species". United States. doi:10.1073/pnas.1715954115.
@article{osti_1416221,
title = {Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species},
author = {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.},
abstractNote = {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 diversity 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.},
doi = {10.1073/pnas.1715954115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 4,
volume = 115,
place = {United States},
year = {2018},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1715954115

Citation Metrics:
Cited by: 7 works
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Figures / Tables:

Table 1 Table 1: Overview of sequencing and annotation data for the four investigated PacBio-sequenced species, plus two additional Illumina-sequenced species

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