skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

This content will become publicly available on February 27, 2021

Title: A comparative genomics study of 23 Aspergillus species from section Flavi

Abstract

Section Flavi encompasses both important harmful and beneficial Aspergillus species. The best known are A. oryzae used in food fermentation and enzyme production and A. flavus, a food and feed spoiler and mycotoxin producer. Here, we have de novo sequenced 19 genomes spanning the breadth of the Flavi section and made comparisons of 31 fungal genomes including 23 section Flavi species to investigate the genomic diversity of this section. Genome analysis shows a high diversity, and identifies islands of diversity in the genomes, including sub-telomeric regions, as the major loci of genetic diversity. Genome-scale phylogeny across the section shows that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans. Addressing food fermentation and industrial biotechnology, we have predicted 13,759 CAZymes (598/species) in section Flavi. The CAZyme content was compared with growth experiments on 35 media showing that the variations in gene content are not necessarily reflected in the growth patterns. Of particular interest is CAZyme family GH28, which is relevant to food fermentation and generally highly expanded in section Flavi, suggesting a part of the success of this section for traditional food production. Addressing fungal safety and potentials for discovery of bioactive compounds,more » we identified 1,606 secondary metabolite gene clusters in section Flavi, (73/species). This is a very high abundance and shows that section Flavi is much more prolific than comparable species such as Aspergillus section Nigri and Penicillium species. Each species has on average >5 clusters found in none of the other species; in total 130 gene clusters are only found in a single species. We have further assigned clusters to 20 types of compounds across 29 species. E.g. for the highly toxic aflatoxin, the gene cluster is highly conserved in 14 section Flavi species, a truncated version is found in A. caelatus, and a complete loss has happened in A. tamarii. By coupling the cluster predictions to chemical data, we have identified a putative miyakamide biosynthetic gene cluster demonstrating one of the versatile possibilities unlocked from this data. In summary, we have generated a highly valuable and versatile resource and used it to demonstrate the diversity and similarities within section Flavi both in terms of CAZyme content and secondary metabolite potential.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1];  [1];  [4];  [4];  [5];  [6];  [7];  [8];  [9];  [10];  [11] more »;  [8];  [10];  [12];  [13];  [14];  [10];  [15];  [16]; ORCiD logo [17];  [18];  [1];  [1];  [4];  [10];  [19]; ORCiD logo [17];  [1] « less
  1. Technical University of Denmark
  2. DOE JGI PGF
  3. Kikkoman Company
  4. Universiteit Utrecht
  5. Westerdijk Fungal Biodiversity Institute, Utrecht University
  6. University of Helsinki
  7. Department of Energy Joint Genome Institute
  8. DOE JGI
  9. Energy Joint Genome Institute
  10. Joint Genome Institute
  11. Lawrence Berkeley National Laboratory
  12. DOE Joint Genome Institute
  13. 2U.S. Department of Energy Joint Genome Institute,
  14. LBNL/JGI
  15. US DOE Joint Genome Institute
  16. Joint BioEnergy Institute
  17. BATTELLE (PACIFIC NW LAB)
  18. AFMB UMR Marseille, France
  19. MULTIPLE CONTRACTORS
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1605144
Report Number(s):
[PNNL-SA-146998]
Grant/Contract Number:  
[AC05-76RL01830]
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
[ Journal Volume: 11; Journal Issue: 1]
Country of Publication:
United States
Language:
English
Subject:
Aspergillus, Section Flavi, Comparative Genomics, Secondary Metabolism, aflatoxin, miyakamide, CAZyme

Citation Formats

Kjaerbolling, Inge, Vesth, Tammi C., Frisvad, Jens, Nybo, Jane, Theobald, Sebastian, Kildgaard, Sara, Petersen, Thomas I., Kuo, Alan, Sato, Atusushi, Lyhne, Ellen, Kogle, Martin E., Wiebenga, Ad, Kun, Roland S., Lubbers, Ronnie J.M., Makela, Miia, Barry, Kerrie W., Chovatia, Mansi, Clum, Alicia, Daum, Christopher, Haridas, Sajeet, He, Guifen, LaButti, Kurt M., Lipzen, Anna, Mondo, Stephen J., Pangilinan, Jasmyn, Riley, Robert, Salamov, Asaf, Simmons, Blake A., Magnuson, Jon K., Henrissat, Bernard, Mortensen, Uffe H., Larsen, Thomas O., de Vries, Ronald P., Grigoriev, Igor V., Machida, Masayuki, Baker, Scott E., and Andersen, Mikael R. A comparative genomics study of 23 Aspergillus species from section Flavi. United States: N. p., 2020. Web. doi:10.1038/s41467-019-14051-y.
Kjaerbolling, Inge, Vesth, Tammi C., Frisvad, Jens, Nybo, Jane, Theobald, Sebastian, Kildgaard, Sara, Petersen, Thomas I., Kuo, Alan, Sato, Atusushi, Lyhne, Ellen, Kogle, Martin E., Wiebenga, Ad, Kun, Roland S., Lubbers, Ronnie J.M., Makela, Miia, Barry, Kerrie W., Chovatia, Mansi, Clum, Alicia, Daum, Christopher, Haridas, Sajeet, He, Guifen, LaButti, Kurt M., Lipzen, Anna, Mondo, Stephen J., Pangilinan, Jasmyn, Riley, Robert, Salamov, Asaf, Simmons, Blake A., Magnuson, Jon K., Henrissat, Bernard, Mortensen, Uffe H., Larsen, Thomas O., de Vries, Ronald P., Grigoriev, Igor V., Machida, Masayuki, Baker, Scott E., & Andersen, Mikael R. A comparative genomics study of 23 Aspergillus species from section Flavi. United States. doi:10.1038/s41467-019-14051-y.
Kjaerbolling, Inge, Vesth, Tammi C., Frisvad, Jens, Nybo, Jane, Theobald, Sebastian, Kildgaard, Sara, Petersen, Thomas I., Kuo, Alan, Sato, Atusushi, Lyhne, Ellen, Kogle, Martin E., Wiebenga, Ad, Kun, Roland S., Lubbers, Ronnie J.M., Makela, Miia, Barry, Kerrie W., Chovatia, Mansi, Clum, Alicia, Daum, Christopher, Haridas, Sajeet, He, Guifen, LaButti, Kurt M., Lipzen, Anna, Mondo, Stephen J., Pangilinan, Jasmyn, Riley, Robert, Salamov, Asaf, Simmons, Blake A., Magnuson, Jon K., Henrissat, Bernard, Mortensen, Uffe H., Larsen, Thomas O., de Vries, Ronald P., Grigoriev, Igor V., Machida, Masayuki, Baker, Scott E., and Andersen, Mikael R. Thu . "A comparative genomics study of 23 Aspergillus species from section Flavi". United States. doi:10.1038/s41467-019-14051-y.
@article{osti_1605144,
title = {A comparative genomics study of 23 Aspergillus species from section Flavi},
author = {Kjaerbolling, Inge and Vesth, Tammi C. and Frisvad, Jens and Nybo, Jane and Theobald, Sebastian and Kildgaard, Sara and Petersen, Thomas I. and Kuo, Alan and Sato, Atusushi and Lyhne, Ellen and Kogle, Martin E. and Wiebenga, Ad and Kun, Roland S. and Lubbers, Ronnie J.M. and Makela, Miia and Barry, Kerrie W. and Chovatia, Mansi and Clum, Alicia and Daum, Christopher and Haridas, Sajeet and He, Guifen and LaButti, Kurt M. and Lipzen, Anna and Mondo, Stephen J. and Pangilinan, Jasmyn and Riley, Robert and Salamov, Asaf and Simmons, Blake A. and Magnuson, Jon K. and Henrissat, Bernard and Mortensen, Uffe H. and Larsen, Thomas O. and de Vries, Ronald P. and Grigoriev, Igor V. and Machida, Masayuki and Baker, Scott E. and Andersen, Mikael R.},
abstractNote = {Section Flavi encompasses both important harmful and beneficial Aspergillus species. The best known are A. oryzae used in food fermentation and enzyme production and A. flavus, a food and feed spoiler and mycotoxin producer. Here, we have de novo sequenced 19 genomes spanning the breadth of the Flavi section and made comparisons of 31 fungal genomes including 23 section Flavi species to investigate the genomic diversity of this section. Genome analysis shows a high diversity, and identifies islands of diversity in the genomes, including sub-telomeric regions, as the major loci of genetic diversity. Genome-scale phylogeny across the section shows that the closest relative of A. oryzae is not A. flavus, but A. minisclerotigenes or A. aflatoxiformans. Addressing food fermentation and industrial biotechnology, we have predicted 13,759 CAZymes (598/species) in section Flavi. The CAZyme content was compared with growth experiments on 35 media showing that the variations in gene content are not necessarily reflected in the growth patterns. Of particular interest is CAZyme family GH28, which is relevant to food fermentation and generally highly expanded in section Flavi, suggesting a part of the success of this section for traditional food production. Addressing fungal safety and potentials for discovery of bioactive compounds, we identified 1,606 secondary metabolite gene clusters in section Flavi, (73/species). This is a very high abundance and shows that section Flavi is much more prolific than comparable species such as Aspergillus section Nigri and Penicillium species. Each species has on average >5 clusters found in none of the other species; in total 130 gene clusters are only found in a single species. We have further assigned clusters to 20 types of compounds across 29 species. E.g. for the highly toxic aflatoxin, the gene cluster is highly conserved in 14 section Flavi species, a truncated version is found in A. caelatus, and a complete loss has happened in A. tamarii. By coupling the cluster predictions to chemical data, we have identified a putative miyakamide biosynthetic gene cluster demonstrating one of the versatile possibilities unlocked from this data. In summary, we have generated a highly valuable and versatile resource and used it to demonstrate the diversity and similarities within section Flavi both in terms of CAZyme content and secondary metabolite potential.},
doi = {10.1038/s41467-019-14051-y},
journal = {Nature Communications},
number = [1],
volume = [11],
place = {United States},
year = {2020},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on February 27, 2021
Publisher's Version of Record

Save / Share:

Works referenced in this record:

Genomics of Aspergillus oryzae: Learning from the History of Koji Mold and Exploration of Its Future
journal, May 2008


Genomics of Aspergillus oryzae
journal, March 2007

  • Kobayashi, Tetsuo; Abe, Keietsu; Asai, Kiyoshi
  • Bioscience, Biotechnology, and Biochemistry, Vol. 71, Issue 3
  • DOI: 10.1271/bbb.60550

Aspergillus flavus: human pathogen, allergen and mycotoxin producer
journal, June 2007


Genome sequencing and analysis of Aspergillus oryzae
journal, December 2005

  • Machida, Masayuki; Asai, Kiyoshi; Sano, Motoaki
  • Nature, Vol. 438, Issue 7071
  • DOI: 10.1038/nature04300

Draft Genome Sequence of an Aflatoxigenic Aspergillus Species, A. bombycis
journal, September 2016

  • Moore, Geromy G.; Mack, Brian M.; Beltz, Shannon B.
  • Genome Biology and Evolution, Vol. 8, Issue 11
  • DOI: 10.1093/gbe/evw238

Investigation of inter- and intraspecies variation through genome sequencing of Aspergillus section Nigri
journal, October 2018


Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species
journal, January 2018

  • Kjærbølling, Inge; Vesth, Tammi C.; Frisvad, Jens C.
  • Proceedings of the National Academy of Sciences, Vol. 115, Issue 4
  • DOI: 10.1073/pnas.1715954115

BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs
journal, June 2015


Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae
journal, December 2005

  • Galagan, James E.; Calvo, Sarah E.; Cuomo, Christina
  • Nature, Vol. 438, Issue 7071
  • DOI: 10.1038/nature04341

New and revisited species in Aspergillus section Nigri
journal, June 2011


Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles
journal, September 2016


CVTree: a phylogenetic tree reconstruction tool based on whole genomes
journal, July 2004

  • Qi, J.; Luo, H.; Hao, B.
  • Nucleic Acids Research, Vol. 32, Issue Web Server
  • DOI: 10.1093/nar/gkh362

InterPro in 2017—beyond protein family and domain annotations
journal, November 2016

  • Finn, Robert D.; Attwood, Teresa K.; Babbitt, Patricia C.
  • Nucleic Acids Research, Vol. 45, Issue D1
  • DOI: 10.1093/nar/gkw1107

Gene Ontology: tool for the unification of biology
journal, May 2000

  • Ashburner, Michael; Ball, Catherine A.; Blake, Judith A.
  • Nature Genetics, Vol. 25, Issue 1
  • DOI: 10.1038/75556

The COG database: an updated version includes eukaryotes
journal, January 2003

  • Tatusov, Roman L.; Fedorova, Natalie D.; Jackson, John D.
  • BMC Bioinformatics, Vol. 4, Article No. 41
  • DOI: 10.1186/1471-2105-4-41

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus
journal, December 2005

  • Nierman, William C.; Pain, Arnab; Anderson, Michael J.
  • Nature, Vol. 438, Issue 7071, p. 1151-1156
  • DOI: 10.1038/nature04332

Genomic Islands in the Pathogenic Filamentous Fungus Aspergillus fumigatus
journal, April 2008

  • Fedorova, Natalie D.; Khaldi, Nora; Joardar, Vinita S.
  • PLoS Genetics, Vol. 4, Issue 4, Article No. e1000046
  • DOI: 10.1371/journal.pgen.1000046

Horizontal gene transfer in fungi
journal, December 2011


Closely related fungi employ diverse enzymatic strategies to degrade plant biomass
journal, August 2015

  • Benoit, Isabelle; Culleton, Helena; Zhou, Miaomiao
  • Biotechnology for Biofuels, Vol. 8, Issue 1
  • DOI: 10.1186/s13068-015-0285-0

Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina)
journal, May 2008

  • Martinez, Diego; Berka, Randy M.; Henrissat, Bernard
  • Nature Biotechnology, Vol. 26, Issue 5
  • DOI: 10.1038/nbt1403

Transcriptome analysis of Aspergillus niger grown on sugarcane bagasse
journal, January 2011

  • de Souza, Wagner R.; de Gouvea, Paula F.; Savoldi, Marcela
  • Biotechnology for Biofuels, Vol. 4, Issue 1
  • DOI: 10.1186/1754-6834-4-40

SMURF: Genomic mapping of fungal secondary metabolite clusters
journal, September 2010

  • Khaldi, Nora; Seifuddin, Fayaz T.; Turner, Geoff
  • Fungal Genetics and Biology, Vol. 47, Issue 9
  • DOI: 10.1016/j.fgb.2010.06.003

Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species
journal, April 2017

  • Nielsen, Jens Christian; Grijseels, Sietske; Prigent, Sylvain
  • Nature Microbiology, Vol. 2, Issue 6
  • DOI: 10.1038/nmicrobiol.2017.44

Minimum Information about a Biosynthetic Gene cluster
journal, August 2015

  • Medema, Marnix H.; Kottmann, Renzo; Yilmaz, Pelin
  • Nature Chemical Biology, Vol. 11, Issue 9
  • DOI: 10.1038/nchembio.1890

Accurate prediction of secondary metabolite gene clusters in filamentous fungi
journal, December 2012

  • Andersen, M. R.; Nielsen, J. B.; Klitgaard, A.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 1
  • DOI: 10.1073/pnas.1205532110

Characterization of a Silent Azaphilone Gene Cluster from Aspergillus niger ATCC 1015 Reveals a Hydroxylation-Mediated Pyran-Ring Formation
journal, August 2012


Low-Volume Toolbox for the Discovery of Immunosuppressive Fungal Secondary Metabolites
journal, April 2013


Identification of a Hybrid PKS/NRPS Required for Pseurotin A Biosynthesis in the Human PathogenAspergillus fumigatus
journal, September 2007


Microprep protocol for extraction of DNA from tomato and other herbaceous plants
journal, September 1995

  • Fulton, Theresa M.; Chunwongse, Julapark; Tanksley, Steven D.
  • Plant Molecular Biology Reporter, Vol. 13, Issue 3
  • DOI: 10.1007/BF02670897

Genomic adaptations of the halophilic Dead Sea filamentous fungus Eurotium rubrum
journal, May 2014

  • Kis-Papo, Tamar; Weig, Alfons R.; Riley, Robert
  • Nature Communications, Vol. 5, Issue 1
  • DOI: 10.1038/ncomms4745

MycoCosm portal: gearing up for 1000 fungal genomes
journal, December 2013

  • Grigoriev, Igor V.; Nikitin, Roman; Haridas, Sajeet
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1183

The carbohydrate-active enzymes database (CAZy) in 2013
journal, November 2013

  • Lombard, Vincent; Golaconda Ramulu, Hemalatha; Drula, Elodie
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1178

The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics
journal, January 2009

  • Cantarel, B. L.; Coutinho, P. M.; Rancurel, C.
  • Nucleic Acids Research, Vol. 37, Issue Database
  • DOI: 10.1093/nar/gkn663

Easyfig: a genome comparison visualizer
journal, January 2011


A New Black Aspergillus Species, A. vadensis, Is a Promising Host for Homologous and Heterologous Protein Production
journal, July 2004


The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources
journal, November 2011

  • Arnaud, M. B.; Cerqueira, G. C.; Inglis, D. O.
  • Nucleic Acids Research, Vol. 40, Issue D1
  • DOI: 10.1093/nar/gkr875

Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88
journal, May 2011

  • Andersen, M. R.; Salazar, M. P.; Schaap, P. J.
  • Genome Research, Vol. 21, Issue 6, p. 885-897
  • DOI: 10.1101/gr.112169.110

The genome sequence of the filamentous fungus Neurospora crassa
journal, April 2003

  • Galagan, James E.; Calvo, Sarah E.; Borkovich, Katherine A.
  • Nature, Vol. 422, Issue 6934
  • DOI: 10.1038/nature01554

APE: Analyses of Phylogenetics and Evolution in R language
journal, January 2004


RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies
journal, January 2014


MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004

  • Edgar, R. C.
  • Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
  • DOI: 10.1093/nar/gkh340

Selection of Conserved Blocks from Multiple Alignments for Their Use in Phylogenetic Analysis
journal, April 2000