In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei

Sorbicillinoids are a diverse group of yellow secondary metabolites that are produced by a range of not closely related ascomycetes, including Penicillium chrysogenum, Acremonium chrysogenum, and Trichoderma reesei. They share a similarity to the name-giving compound sorbicillin, a hexaketide. Previ...

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Main Authors: Christian Derntl, Fernando Guzmán-Chávez, Thiago M. Mello-de-Sousa, Hans-Jürgen Busse, Arnold J. M. Driessen, Robert L. Mach, Astrid R. Mach-Aigner
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fmicb.2017.02037/full
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author Christian Derntl
Fernando Guzmán-Chávez
Thiago M. Mello-de-Sousa
Hans-Jürgen Busse
Arnold J. M. Driessen
Robert L. Mach
Astrid R. Mach-Aigner
author_facet Christian Derntl
Fernando Guzmán-Chávez
Thiago M. Mello-de-Sousa
Hans-Jürgen Busse
Arnold J. M. Driessen
Robert L. Mach
Astrid R. Mach-Aigner
author_sort Christian Derntl
collection DOAJ
description Sorbicillinoids are a diverse group of yellow secondary metabolites that are produced by a range of not closely related ascomycetes, including Penicillium chrysogenum, Acremonium chrysogenum, and Trichoderma reesei. They share a similarity to the name-giving compound sorbicillin, a hexaketide. Previously, a conserved gene cluster containing two polyketide synthases has been identified as the source of sorbicillin, and a model for the biosynthesis of sorbicillin in P. chrysogenum has been proposed. In this study, we deleted the major genes of interest of the cluster in T. reesei, namely sor1, sor3, and sor4. Sor1 is the homolog of P. chrysogenum SorA, which is the first polyketide synthase of the proposed biosynthesis pathway. Sor3 is a flavin adenine dinucleotide (FAD)-dependent monooxygenase, and its homolog in P. chrysogenum, SorC, was shown to oxidize sorbicillin and 2′,3′-dihydrosorbicillin to sorbicillinol and 2′,3′-dihydrosorbicillinol, respectively, in vitro. Sor4 is an FAD/flavin mononucleotide-containing dehydrogenase with an unknown function. We measured the amounts of synthesized sorbicillinoids throughout growth and could verify the roles of Sor1 and Sor3 in vivo in T. reesei. In the absence of Sor4, two compounds annotated to dihydrosorbicillinol accumulate in the supernatant and only small amounts of sorbicillinol are synthesized. Therefore, we suggest extending the current biosynthesis model about Sor4 reducing 2′,3′-dihydrosorbicillin and 2′,3′-dihydrosorbicillinol to sorbicillinol and sorbicillinol, respectively. Sorbicillinol turned out to be the main chemical building block for most sorbicillinoids, including oxosorbicillinol, bisorbicillinol, and bisvertinolon. Further, we detected the sorbicillinol-dependent synthesis of 5-hydroxyvertinolide at early time points, which contradicts previous models for biosynthesis of 5-hydroxyvertinolide. Finally, we investigated whether sorbicillinoids from T. reesei have a growth limiting effect on the fungus itself or on plant pathogenic fungi or on pathogenic bacteria.
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spelling doaj.art-bae3ba26800f46aabce72e3940932eaf2022-12-22T03:06:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-10-01810.3389/fmicb.2017.02037270392In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reeseiChristian Derntl0Fernando Guzmán-Chávez1Thiago M. Mello-de-Sousa2Hans-Jürgen Busse3Arnold J. M. Driessen4Robert L. Mach5Astrid R. Mach-Aigner6Research Area Biochemical Technology, Institute of Chemical, Environmental & Biological Engineering, Vienna, AustriaMolecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsResearch Area Biochemical Technology, Institute of Chemical, Environmental & Biological Engineering, Vienna, AustriaInstitute of Microbiology, University of Veterinary Medicine, Vienna, AustriaMolecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsResearch Area Biochemical Technology, Institute of Chemical, Environmental & Biological Engineering, Vienna, AustriaResearch Area Biochemical Technology, Institute of Chemical, Environmental & Biological Engineering, Vienna, AustriaSorbicillinoids are a diverse group of yellow secondary metabolites that are produced by a range of not closely related ascomycetes, including Penicillium chrysogenum, Acremonium chrysogenum, and Trichoderma reesei. They share a similarity to the name-giving compound sorbicillin, a hexaketide. Previously, a conserved gene cluster containing two polyketide synthases has been identified as the source of sorbicillin, and a model for the biosynthesis of sorbicillin in P. chrysogenum has been proposed. In this study, we deleted the major genes of interest of the cluster in T. reesei, namely sor1, sor3, and sor4. Sor1 is the homolog of P. chrysogenum SorA, which is the first polyketide synthase of the proposed biosynthesis pathway. Sor3 is a flavin adenine dinucleotide (FAD)-dependent monooxygenase, and its homolog in P. chrysogenum, SorC, was shown to oxidize sorbicillin and 2′,3′-dihydrosorbicillin to sorbicillinol and 2′,3′-dihydrosorbicillinol, respectively, in vitro. Sor4 is an FAD/flavin mononucleotide-containing dehydrogenase with an unknown function. We measured the amounts of synthesized sorbicillinoids throughout growth and could verify the roles of Sor1 and Sor3 in vivo in T. reesei. In the absence of Sor4, two compounds annotated to dihydrosorbicillinol accumulate in the supernatant and only small amounts of sorbicillinol are synthesized. Therefore, we suggest extending the current biosynthesis model about Sor4 reducing 2′,3′-dihydrosorbicillin and 2′,3′-dihydrosorbicillinol to sorbicillinol and sorbicillinol, respectively. Sorbicillinol turned out to be the main chemical building block for most sorbicillinoids, including oxosorbicillinol, bisorbicillinol, and bisvertinolon. Further, we detected the sorbicillinol-dependent synthesis of 5-hydroxyvertinolide at early time points, which contradicts previous models for biosynthesis of 5-hydroxyvertinolide. Finally, we investigated whether sorbicillinoids from T. reesei have a growth limiting effect on the fungus itself or on plant pathogenic fungi or on pathogenic bacteria.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02037/fullsorbicillinoidssorbicillinol5-hydroxyvertinolideTrichoderma reeseiAcremonium chrysogenumPenicillium chrysogenum
spellingShingle Christian Derntl
Fernando Guzmán-Chávez
Thiago M. Mello-de-Sousa
Hans-Jürgen Busse
Arnold J. M. Driessen
Robert L. Mach
Astrid R. Mach-Aigner
In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
Frontiers in Microbiology
sorbicillinoids
sorbicillinol
5-hydroxyvertinolide
Trichoderma reesei
Acremonium chrysogenum
Penicillium chrysogenum
title In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
title_full In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
title_fullStr In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
title_full_unstemmed In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
title_short In Vivo Study of the Sorbicillinoid Gene Cluster in Trichoderma reesei
title_sort in vivo study of the sorbicillinoid gene cluster in trichoderma reesei
topic sorbicillinoids
sorbicillinol
5-hydroxyvertinolide
Trichoderma reesei
Acremonium chrysogenum
Penicillium chrysogenum
url http://journal.frontiersin.org/article/10.3389/fmicb.2017.02037/full
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