reposiTUm: Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei

DC Field

Value

Language

dc.contributor.author

Burger, Isabella

dc.contributor.author

Schmal, Matthias

dc.contributor.author

Fourtis, Lukas

dc.contributor.author

Peikert, Kathrin

dc.contributor.author

Suster, Christoph

dc.contributor.author

Stanetty, Christian

dc.contributor.author

Schnalzer, Dominik

dc.contributor.author

Birner-Grünberger, Ruth

dc.contributor.author

Mach, Robert

dc.contributor.author

Mach-Aigner, Astrid

dc.contributor.author

Derntl, Christian

dc.contributor.author

Schittmayer-Schantl, Matthias

dc.date.accessioned

2025-01-02T16:04:07Z

dc.date.available

2025-01-02T16:04:07Z

dc.date.issued

2024-09-23

dc.identifier.citation

<div class="csl-bib-body"> <div class="csl-entry">Burger, I., Schmal, M., Fourtis, L., Peikert, K., Suster, C., Stanetty, C., Schnalzer, D., Birner-Grünberger, R., Mach, R., Mach-Aigner, A., Derntl, C., & Schittmayer-Schantl, M. (2024, September 23). <i>Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei</i> [Conference Presentation]. APMRS/CEEPC APMRS-CEEPC 2024, Wien, Austria. http://hdl.handle.net/20.500.12708/207567</div> </div>

dc.identifier.uri

http://hdl.handle.net/20.500.12708/207567

dc.description.abstract

Introduction In the quest to discover novel antifungal agents and new antifungal production processes, we investigated the biosynthetic gene cluster (BGC) for ilicicolin H in the fungus Trichoderma reesei. While the BGC is silent under standard cultivation conditions, we achieved to activate it by over-expressing its transcription factor TriliR. Methods Successful BGC activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. Molecular networking led to the identification of related ilicicolin products. Results and Discussion Metabolomic profiling upon BGC expression revealed high-yield production of the supposed main product ilicicolin H. To elucidate the functionality of this BGC, we employed a combination of overexpression and deletions of individual biosynthetic gene cluster constituents. Deletion of triliA, encoding for the core polyketide synthase TriliA, completely ceased product formation, as expected. In contrast to previous heterologous expression experiments, we could demonstrate that the epimerase TriliE is necessary for the formation of ilicicolin H in the native host. While we hardly observed any of the previously reported side- or shunt products associated with heterologous ilicicolin H expression, we discovered a novel member of the ilicicolin family using a metabolomic molecular networking approach. This new compound, which we termed ilicicolin K, is expressed in substantial amounts in the genetically engineered Trichoderma reesei, enabling us to elucidate its structure by NMR. The structure of ilicicolin K is similar to that of ilicicolin H but differs by an additional hydroxylation and an intramolecular etherification of the hydroxyl group at the pyridine towards the tyrosine moiety of the molecule. Initial tests of ilicicolin K showed antifungal activity against Saccharomyces cerevisiae and Aspergillus nidulans with a similar minimum inhibitory concentration as ilicicolin H. Innovative aspects • High-yield expression of ilicicolin H by genetic BGC activation in a native host for the first time • Discovery of a novel antifungal compound, ilicicolin K

dc.description.sponsorship

FWF - Österr. Wissenschaftsfonds

dc.language.iso

dc.subject

natural product

dc.subject

mass spectrometry

dc.subject

NMR spectroscopy

dc.title

Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei

dc.type

Presentation

dc.type

Vortrag

dc.contributor.affiliation

TU Wien, Austria

dc.contributor.affiliation

TU Wien, Austria

dc.relation.grantno

P 34036-B

dc.type.category

Conference Presentation

tuw.publication.invited

invited

tuw.project.title

Identifizierung und Charakterisierung von RiPPs aus Pilzen

tuw.researchinfrastructure

Zentrum für Kernspinresonanzspektroskopie

tuw.researchTopic.id

tuw.researchTopic.name

Biological and Bioactive Materials

tuw.researchTopic.value

100

tuw.publication.orgunit

E164-01-3 - Forschungsgruppe Bioanalytik

tuw.publication.orgunit

E166-05-1 - Forschungsgruppe Synthetische Biologie und Molekulare Biotechnologie

tuw.publication.orgunit

E163-03-4 - Forschungsgruppe Bioorganische Synthesechemie

tuw.author.orcid

0000-0001-6419-1270

tuw.author.orcid

0000-0002-3592-4882

tuw.author.orcid

0000-0001-7692-6932

tuw.author.orcid

0009-0003-0469-197X

tuw.author.orcid

0000-0003-3950-0312

tuw.author.orcid

0000-0003-2375-7244

tuw.author.orcid

0000-0002-7575-2317

tuw.author.orcid

0000-0002-6440-2100

tuw.author.orcid

0000-0003-3249-655X

tuw.event.name

APMRS/CEEPC APMRS-CEEPC 2024

tuw.event.startdate

23-09-2024

tuw.event.enddate

25-09-2024

tuw.event.online

On Site

tuw.event.type

Event for scientific audience

tuw.event.place

Wien

tuw.event.country

tuw.event.institution

APMA

tuw.event.presenter

Burger, Isabella

wb.sciencebranch

Chemie

wb.sciencebranch

Pharmazie, Pharmakologie, Toxikologie

wb.sciencebranch

Industrielle Biotechnologie

wb.sciencebranch.oefos

1040

wb.sciencebranch.oefos

3012

wb.sciencebranch.oefos

2090

wb.sciencebranch.value

item.cerifentitytype

Publications

item.languageiso639-1

item.fulltext

no Fulltext

item.openairetype

conference paper not in proceedings

item.openairecristype

http://purl.org/coar/resource_type/c_18cp

item.grantfulltext

none

crisitem.project.funder

FWF - Österr. Wissenschaftsfonds

crisitem.project.grantno

P 34036-B

crisitem.author.dept

E164-01-3 - Forschungsgruppe Bioanalytik

crisitem.author.dept

E166-05-1 - Forschungsgruppe Synthetische Biologie und Molekulare Biotechnologie

crisitem.author.dept

E166-05-1 - Forschungsgruppe Synthetische Biologie und Molekulare Biotechnologie

crisitem.author.dept

E166-05-1 - Forschungsgruppe Synthetische Biologie und Molekulare Biotechnologie

crisitem.author.dept

E163-03-4 - Forschungsgruppe Bioorganische Synthesechemie

crisitem.author.dept

E163-03-4 - Forschungsgruppe Bioorganische Synthesechemie

crisitem.author.dept

E163-03-4 - Forschungsgruppe Bioorganische Synthesechemie

crisitem.author.dept

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

crisitem.author.dept

E166 - Institut für Verfahrenstechnik, Umwelttechnik und technische Biowissenschaften

crisitem.author.dept

E166-05 - Forschungsbereich Biochemische Technologie

crisitem.author.dept

E166-05-1 - Forschungsgruppe Synthetische Biologie und Molekulare Biotechnologie

crisitem.author.dept

E164-01-3 - Forschungsgruppe Bioanalytik

crisitem.author.orcid

0000-0001-6419-1270

crisitem.author.orcid

0000-0002-3592-4882

crisitem.author.orcid

0000-0001-7692-6932

crisitem.author.orcid

0009-0003-0469-197X

crisitem.author.orcid

0000-0003-3950-0312

crisitem.author.orcid

0000-0003-2375-7244

crisitem.author.orcid

0000-0002-7575-2317

crisitem.author.orcid

0000-0002-6440-2100

crisitem.author.orcid

0000-0003-3249-655X

crisitem.author.parentorg

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

crisitem.author.parentorg

E166-05 - Forschungsbereich Biochemische Technologie

crisitem.author.parentorg

E166-05 - Forschungsbereich Biochemische Technologie

crisitem.author.parentorg

E166-05 - Forschungsbereich Biochemische Technologie

crisitem.author.parentorg

E163-03 - Forschungsbereich Organische und Biologische Chemie

crisitem.author.parentorg

E163-03 - Forschungsbereich Organische und Biologische Chemie

crisitem.author.parentorg

E163-03 - Forschungsbereich Organische und Biologische Chemie

crisitem.author.parentorg

E164 - Institut für Chemische Technologien und Analytik

crisitem.author.parentorg

E150 - Fakultät für Technische Chemie

crisitem.author.parentorg

E166 - Institut für Verfahrenstechnik, Umwelttechnik und technische Biowissenschaften

crisitem.author.parentorg

E166-05 - Forschungsbereich Biochemische Technologie

crisitem.author.parentorg

E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie

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