Bioprospecting of natural products in fungi

  • Synthetic biology
  • Molecular and functional genetics
  • Identification and expression of cryptic secondary metabolite gene clusters
  • Regulation of secondary metabolites

Natural products are an inestimable source of active compounds. Fungi have the capacity to produce very diverse spectra of chemicals that can be potentially used as therapeutics, or for biological control of plant pests. With the beginning of the genomic era, secondary metabolite biosynthetic pathways can be predicted by genome mining. These pathways can be isolated and heterologously expressed in amenable organisms to identify new metabolites. Such an approach is more powerful than stochastically trying to activate chemical biosynthesis in lab conditions.

The isolation and structure elucidation of new chemicals can be theoretically used to assign a function to these molecules and to understand their ecological meaning. This approach is not only suitable to increase knowledge about chemical diversity, but can be exploited to uncover the natural role of concealed secondary metabolites.


Vito Valiante


In cooperation with partners from the Leibniz Research Cluster we are building cell free biosynthetic systems. Enzymes responsible for specific reactions are isolated and purified, and subsequently immobilized on synthetic polymers. This cell free approach will be optimized in order to obtain complex active molecules starting from simple chemical units.

Cryptic gene clusters

Learning from Picornaviruses, we exploited 2A peptides to express entire biosynthetic pathways as single polycistronic genes. Assembling plasmids and read out systems were developed in order to efficiently screen transformed recipient organisms.

Cryptic gene clusters

Signalling pathways

Environmental changes are sensed by fungi and transduced via signal transduction pathways. Comparative studies highlighted that MAPKs, calmodulin/calcineurin, TOR and Ras/cAMP signalling pathways are well conserved in eukaryotic organisms. Our goal is to elucidate the meaning of signal transduction pathways for gene regulation.


Jojić K*, Gherlone F*, Cseresnyés Z, Bissell AU, Hoefgen S, Hoffmann S, Huang Y, Janevska S, Figge MT, Valiante V (2024) The spatial organization of sphingofungin biosynthesis in Aspergillus fumigatus and its cross-interaction with sphingolipid metabolism. mBio 15(3), e0019524.
Valiante V (2023) Advances in synthetic biology of fungi and contributions to the discovery of new molecules. ChemBioChem 24(11), e202300008. (Review)
Bissell AU, Rautschek J, Hoefgen S, Raguž L, Mattern DJ, Saeed N, Janevska S, Jojić K, Huang Y, Kufs JE, Herboeck B, Guo H, Hillmann F, Beemelmanns C, Valiante V (2022) Biosynthesis of the sphingolipid inhibitors sphingofungins in filamentous fungi requires aminomalonate as a metabolic precursor. ACS Chem Biol 17(2), 386-394.
Günther M*, Reimer C*, Herbst R*, Kufs JE, Rautschek J, Ueberschaar N, Zhang S, Peschel G, Reimer L, Regestein L, Valiante V, Hillmann F#, Stallforth P# (2022) Yellow polyketide pigment suppresses premature hatching in social amoeba. Proc Natl Acad Sci U S A 119(43), e2116122119.
Hoefgen S, Bissell AU, Huang Y, Gherlone F, Raguž L, Beemelmanns C, Valiante V (2022) Desaturation of the sphingofungin polyketide tail results in increased serine palmitoyltransferase inhibition. Microbiol Spectr 10(5), e0133122.
Huang Y*, Hoefgen S*, Gherlone F, Valiante V (2022) Intrinsic ability of the ß-oxidation pathway to produce bioactive styrylpyrones. Angew Chem Int Ed 61(34), e202206851.
Kufs JE, Reimer C, Steyer E, Valiante V, Hillmann F, Regestein L (2022) Scale-up of an amoeba-based process for the production of the cannabinoid precursor olivetolic acid. Microb Cell Fact 21(1), 217.
Maehler D, Hoefgen S, Münchberg U, Schmitz OJ, Rautschek J, Huang Y, Freier E, Valiante V (2022) Time-resolved multiparameter analytics on a cell-free production platform for acyl-CoA precursors. Anal Sci Adv 3, 289-296.
Reimer C*, Kufs JE*, Rautschek J, Regestein L, Valiante V#, Hillmann F# (2022) Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides. Nat Biotechnol 40(5), 751-758.
Huang Y, Höfgen S, Valiante V (2021) Biosynthesis of fungal drimane-type sesquiterpene esters. Angew Chem Int Ed 60(44), 23763-23770.