Heterologous Expression of the Unusual Terreazepine Biosynthetic Gene Cluster Reveals a Promising Approach for Identifying New Chemical Scaffolds.

Aspergillus Aspergillus nidulans Aspergillus terreus IDO NRPS biosynthetic gene cluster genome mining heterologous expression indoleamine 2,3-dioxygenase kynurenine natural products

Journal

mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231

Informations de publication

Date de publication:
25 08 2020
Historique:
entrez: 27 8 2020
pubmed: 28 8 2020
medline: 16 7 2021
Statut: epublish

Résumé

Advances in genome sequencing have revitalized natural product discovery efforts, revealing the untapped biosynthetic potential of fungi. While the volume of genomic data continues to expand, discovery efforts are slowed due to the time-consuming nature of experiments required to characterize new molecules. To direct efforts toward uncharacterized biosynthetic gene clusters most likely to encode novel chemical scaffolds, we took advantage of comparative metabolomics and heterologous gene expression using fungal artificial chromosomes (FACs). By linking mass spectral profiles with structural clues provided by FAC-encoded gene clusters, we targeted a compound originating from an unusual gene cluster containing an indoleamine 2,3-dioxygenase (IDO). With this approach, we isolate and characterize

Identifiants

pubmed: 32843555
pii: mBio.01691-20
doi: 10.1128/mBio.01691-20
pmc: PMC7448278
pii:
doi:

Substances chimiques

Biological Products 0
Kynurenine 343-65-7

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : F32 GM134679
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI065728
Pays : United States
Organisme : NCCIH NIH HHS
ID : R44 AT009158
Pays : United States

Informations de copyright

Copyright © 2020 Caesar et al.

Références

Biochim Biophys Acta. 2013 Jun;1830(6):3670-95
pubmed: 23428572
Biochemistry. 2018 Jun 12;57(23):3237-3243
pubmed: 29533658
Nat Chem Biol. 2017 Aug;13(8):895-901
pubmed: 28604695
Microbiology (Reading). 2005 May;151(Pt 5):1507-1523
pubmed: 15870461
Anal Chem. 2015 Jul 7;87(13):6520-6
pubmed: 26020678
ACS Chem Biol. 2018 May 18;13(5):1142-1147
pubmed: 29631395
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17462-7
pubmed: 17090667
Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):E99-107
pubmed: 23248299
PLoS One. 2015 Apr 23;10(4):e0124459
pubmed: 25905794
ACS Chem Biol. 2016 Aug 19;11(8):2275-84
pubmed: 27294372
Nat Prod Rep. 2014 Oct;31(10):1425-48
pubmed: 25122538
Med Princ Pract. 2016;25 Suppl 2:41-59
pubmed: 26679767
Mol Biol Evol. 2018 Jun 1;35(6):1547-1549
pubmed: 29722887
J Am Chem Soc. 2012 Oct 10;134(40):16781-90
pubmed: 22998630
Curr Med Chem. 2017;24(23):2471-2495
pubmed: 28464785
J Nat Prod. 2016 Mar 25;79(3):629-61
pubmed: 26852623
Org Lett. 2019 Mar 1;21(5):1444-1448
pubmed: 30789272
Amino Acids. 2013 Dec;45(6):1319-29
pubmed: 24105077
Chem Biol. 2011 Feb 25;18(2):148-64
pubmed: 21338914
Nat Chem Biol. 2014 Nov;10(11):963-8
pubmed: 25262415
Biochemistry. 2006 Dec 19;45(50):15029-38
pubmed: 17154540
Nat Rev Microbiol. 2005 Dec;3(12):937-47
pubmed: 16322742
J Am Chem Soc. 2013 Mar 27;135(12):4616-9
pubmed: 23488861
Nat Chem Biol. 2020 Jan;16(1):60-68
pubmed: 31768033
Front Immunol. 2018 Jan 22;8:1996
pubmed: 29403477
Angew Chem Int Ed Engl. 2019 Oct 7;58(41):14589-14593
pubmed: 31342608
Org Biomol Chem. 2018 Mar 7;16(10):1620-1626
pubmed: 29393329
Fungal Genet Biol. 2016 Apr;89:18-28
pubmed: 26808821
Nat Rev Microbiol. 2019 Mar;17(3):167-180
pubmed: 30531948
J Antimicrob Chemother. 2005 Mar;55(3):283-8
pubmed: 15705644
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14873-7
pubmed: 8962148
J Am Chem Soc. 2020 Apr 15;142(15):7145-7152
pubmed: 32182055
Biochemistry. 2011 Jun 28;50(25):5680-92
pubmed: 21612226
Clin Sci (Lond). 2015 Oct;129(7):601-72
pubmed: 26186743
J Antibiot (Tokyo). 2011 Jan;64(1):117-22
pubmed: 21102595
Cancer Res. 2017 Dec 15;77(24):6795-6811
pubmed: 29247038
Nucleic Acids Res. 2017 Jul 3;45(W1):W36-W41
pubmed: 28460038
BMC Genomics. 2015 Apr 29;16:343
pubmed: 25925221
Gene. 2012 Aug 1;504(1):64-74
pubmed: 22564706
Curr Opin Chem Biol. 2016 Apr;31:40-9
pubmed: 26812494
Org Lett. 2018 Dec 7;20(23):7633-7636
pubmed: 30474984
Org Biomol Chem. 2013 Nov 21;11(43):7616-20
pubmed: 24104948

Auteurs

Lindsay K Caesar (LK)

Department of Chemistry, Northwestern University, Evanston, Illinois, USA.

Matthew T Robey (MT)

Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.

Michael Swyers (M)

Intact Genomics, Inc., St. Louis, Missouri, USA.

Md N Islam (MN)

Intact Genomics, Inc., St. Louis, Missouri, USA.

Rosa Ye (R)

Intact Genomics, Inc., St. Louis, Missouri, USA.

Purav P Vagadia (PP)

Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA.

Gary E Schiltz (GE)

Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois, USA.
Department of Pharmacology, Northwestern University, Chicago, Illinois, USA.
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Paul M Thomas (PM)

Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.

Chengcang C Wu (CC)

Intact Genomics, Inc., St. Louis, Missouri, USA cwu@intactgenomics.com n-kelleher@northwestern.edu npkeller@wisc.edu jbok@wisc.edu.

Neil L Kelleher (NL)

Department of Chemistry, Northwestern University, Evanston, Illinois, USA cwu@intactgenomics.com n-kelleher@northwestern.edu npkeller@wisc.edu jbok@wisc.edu.
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA.

Nancy P Keller (NP)

Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA cwu@intactgenomics.com n-kelleher@northwestern.edu npkeller@wisc.edu jbok@wisc.edu.
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Jin Woo Bok (JW)

Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA cwu@intactgenomics.com n-kelleher@northwestern.edu npkeller@wisc.edu jbok@wisc.edu.

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Classifications MeSH