**4. Terpenoids**

Terpenoids are synthetized from the acetyl CoA-derived C-5-isopentenyl-diphosphate intermediates isopentenyl- and dimethylallyl-diphosphate. The C-5 units are subsequently processed via head-to-tail condensation by prenyl synthases and are post-synthetically modified by various enzymes resulting in different terpenoids originating from very few C-5 precursors [56]. Terpenoid biosynthetic clusters are characterized by the presence of a terpene cyclase gene [4]. Terpenoids are volatile to non-volatile substances constituting the highest abundant natural products on earth [37]. Terpenoids of fungal origin comprise phytohormones, mycotoxins as well as antibiotics and antitumor substances.

The *C. rosea* genome contains eight terpene synthase genes [51] and *E. weberi* comprises an expansion of six genes for terpene synthases in its genome, of which three lie within unique biosynthetic secondary metabolite clusters [15]. The majority of secondary metabolites of *S. elegans* secreted during mycoparasitizing *R. solani* are trichothezenes and atranones belong to the terpenoid class of secondary metabolites [17]. The *T. virens* genome comprises an enrichment of terpene cyclase genes compared to *T. atroviride* and *T. reesei* [57]. The production of several terpenoids was proven for *Trichoderma* species [58, 59], whereas their biosynthetic pathways mostly still remain obscure. The putative terpene cyclase *vir4* is well-researched and only present in *T. virens,* but not in *T. reesei* or *T. atroviride*. Analysis of a mutant which exhibited defects in antibiotic production, a lack of viridin and viridiol synthesis and an under-expression of most of the genes of the *vir4* cluster evidenced that the cluster is involved in viridin biosynthesis [60]. Generation of a *vir4* deletion mutant and metabolic screening validated its involvement in terpene biosynthesis; the terpene cyclase gene *vir4*, however, turned out not to be involved in viridin or viridiol biosynthesis but in the synthesis of more than 20 volatile sesquiterpenes [61]. The involvement of terpenes in mycoparasitism relies unresolved, but there are hints: it is probable that genes underlying the mevalonate pathway also influence terpene synthesis. The *hmgR* gene codes for the glycoprotein 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, which processes HMG-CoA to mevalonic acid. Accordingly *hmgR-*silenced mutants of *T. harzianum* exhibited decreased antifungal abilities [62]. Deletion of the trichodiene synthase genes *tri4* and *tri5* in *Trichoderma arundinaceum* resulted in a loss of harzianum A production, a reduced antagonism against host fungi and a decreased ISR in tomato plants [63, 64]. Expression of the *T. arundinaceum tri4* and/or *tri5* genes in *T. harzianum* mainly influenced plant wealth and defense by induced production of trichodiene and 12, 13-epoxytrichothec-9-ene (EPT) [65, 66], whereas *tri5* overexpression in *Trichoderma brevicompactum* boosted the excretion of antifungal trichodermin [67, 68].

**3. Polyketides (PKs)**

42 Secondary Metabolites - Sources and Applications

to toxins [2].

**4. Terpenoids**

Polyketides (PKs) are derived from simple building blocks like acetyl-CoA or malonyl-CoA via consecutive PKS-mediated decarboxylative condensation and subsequent post-synthetic modification. Fungal PKSs are complex multi-modular enzymes, which obligatory include a characteristic ketoacyl-CoA-synthase (KS), an acyltransferase (AT) and an acyl-carrier (ACP) domain [20]. The structurally diverse PKs are the main class of secondary metabolites derived from fungi. The spectrum of substances ranges from spore pigments over antibiotics

The *T. virens* and *T. atroviride* genomes are enriched for about 60% in PKS genes compared to *T. reesei* [21]. The *C. rosea* genome even exceeds this number with a total of 31 PKS genes [51], whereas the *T. ophioglossoides* genome comprises 15 PKSs [11]. The TMC-151 type PKs derived from *C. rosea* exhibits antibacterial properties [52], whereas *T. ophioglossoides* produces two antifungal and antibacterial substances: the polyketide ophiocordin and the NRPS-PKS hybrid enzyme-derived ophiosetin [11, 53, 54]. The deletion of *pks4* – encoding an orthologue of the aurofusarin and bikerfusarin forming PKSs of *Fusarium* spp. – in *T. reesei* caused extensive changes in morphology as well as physiology and metabolism. In ∆*pks4* mutants, the pigmentation of conidia and the generation of teleomorph structures were inhibited, and the stability of the conidial cell wall was reduced. *Pks4* deletion decreased *T. reesei'*s antagonistic abilities in confrontation assays, lowered its antifungal effect mediated by water soluble and volatile metabolites and altered the expression pattern of other PKSs [55]. It seems that also within this metabolite class, the effects are more diverse and global, than hitherto expected.

Terpenoids are synthetized from the acetyl CoA-derived C-5-isopentenyl-diphosphate intermediates isopentenyl- and dimethylallyl-diphosphate. The C-5 units are subsequently processed via head-to-tail condensation by prenyl synthases and are post-synthetically modified by various enzymes resulting in different terpenoids originating from very few C-5 precursors [56]. Terpenoid biosynthetic clusters are characterized by the presence of a terpene cyclase gene [4]. Terpenoids are volatile to non-volatile substances constituting the highest abundant natural products on earth [37]. Terpenoids of fungal origin comprise phytohormones, myco-

The *C. rosea* genome contains eight terpene synthase genes [51] and *E. weberi* comprises an expansion of six genes for terpene synthases in its genome, of which three lie within unique biosynthetic secondary metabolite clusters [15]. The majority of secondary metabolites of *S. elegans* secreted during mycoparasitizing *R. solani* are trichothezenes and atranones belong to the terpenoid class of secondary metabolites [17]. The *T. virens* genome comprises an enrichment of terpene cyclase genes compared to *T. atroviride* and *T. reesei* [57]. The production of several terpenoids was proven for *Trichoderma* species [58, 59], whereas their biosynthetic pathways mostly still remain obscure. The putative terpene cyclase *vir4* is well-researched

toxins as well as antibiotics and antitumor substances.
