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

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

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »; ORCiD logo; ; ; ; ; ; ORCiD logo « less
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1416221
Grant/Contract Number:
AC02-05CH11231
Resource Type:
Journal Article: Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 115; Journal Issue: 4; Related Information: CHORUS Timestamp: 2018-01-23 15:02:42; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

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. 2018. "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 = {},
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
This content will become publicly available on July 23, 2018
Publisher's Version of Record

Save / Share:
  • Nonribosomal peptides (NRPs) are natural products biosynthesized by NRP synthetases. A kusA-, pyrG- mutant strain of Aspergillusterreus NIH 2624 was developed that greatly facilitated the gene targeting efficiency in this organism. Application of this tool allowed us to link four major types of NRP related secondary metabolites to their responsible genes in A. terreus. In addition, an NRP related melanin synthetase was also identified in this species.
  • In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG’s comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve asmore » the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC’s focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in lphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG’s extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.« less
  • Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. In this paper, we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains, including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated themore » identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. Finally, these efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches.« less
  • Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. In this paper, we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains, including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated themore » identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. Finally, these efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches.« less
  • Mycotoxins constitute a group of toxic secondary fungal metabolites. Fungi that produce these toxins frequently contaminate food and feed, creating a potential threat to human and animal health. Biological activities of mycotoxins include, amongst others: toxicity, mutagenicity and carcinogenicity, which can be expressed with or without metabolic activation. Austocystins are similar in structure to aflatoxin B/sup 1/ and are probably synthesized in a similar manner. The Ames Salmonella test, a widely accepted method employed for the detection of mutagenic activity of various chemical compounds was used for testing the mutagenic activity of different mycotoxins. As aflatoxin B/sup 1/ was foundmore » by the Ames test to be highly mutagenic, the same test was applied for the study of possible mutagenicity of the austocystins. The mutagenic activity of these compounds was studied with and without metabolic activation using two tester strains of S. typhimurium, one capable of detecting frame shift mutation (strain TA98) and the other capable of detecting base pair substitution (strain TA100).« less