PXD055742

PXD055742 is an original dataset announced via ProteomeXchange.

Title	Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei
Description	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. Successful BGC activation was confirmed by RT-qPCR, proteomic and metabolomic analyses. 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 pyridone 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.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-13_05:28:59.457.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Isabella Burger
SpeciesList	scientific name: Trichoderma reesei; NCBI TaxID: 51453;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-09 06:48:28	ID requested
⏵ 1	2025-03-13 05:28:59	announced

Dataset with its publication pending

submitter keyword: multi-omics,fungi, natural products

Matthias Schittmayer
contact affiliation	TU Wien, Institute of Chemical Technologies and Analytics, 1060 Wien, Austria
contact email	matthias.schittmayer@tuwien.ac.at
lab head
Isabella Burger
contact affiliation	TU Wien, Institute of Chemical Technologies and Analytics
contact email	isabella.burger@tuwien.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055742
     1. Label: PRIDE project
     2. Name: Discovery of a novel antifungal compound, ilicicolin K, through genetic activation of the ilicicolin biosynthetic pathway in Trichoderma reesei