**3. Polyketides (PKs)**

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 to toxins [2].

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

Secondary Metabolites of Mycoparasitic Fungi http://dx.doi.org/10.5772/intechopen.75133 43

*Trichoderma brevicompactum* boosted the excretion of antifungal trichodermin [67, 68].

**5. Ecology and regulation of secondary metabolism in mycoparasitic** 

Ancestral and recent lifestyles fundamentally influence the existence as well as the expression of secondary metabolite genes and clusters up to the species or even strain level. The transcriptional responses of *T. reesei, T. atroviride* and *T. virens –* which all share an ancestral mycoparasitic lifestyle – to the confrontation with *R. solani* illustrates this fact very well. All three species exhibit few common metabolic responses but autonomous and specific strategies in defeating their opponent. Both potent mycoparasites, *T. atroviride* and *T. virens*, attack their hosts in the stage before physical contact, but with distinct strategies of antibiosis. *T. virens* offends mostly via the NRP biosynthetic pathway for gliotoxin synthesis, whereas *T. atroviride* combats mainly via the PKS biosynthetic pathway, as well as the excretion of 6-pentyl-α-pyrone (6-PP) – a volatile organic compound (VOC) with antifungal and plant growth-promoting properties [2]. Conversely, the transcriptional response of the only slightly mycoparasitic *T. reesei* is more defense-related and targeted on the excretion of cellulases, hemicellulases and ribosomal proteins before hyphal contact [69]. The long-term specialized lifestyle and co-evolution of *E. weberi* with its host in its relatively demarcated ecological niche facilitated the loss of a manifold of genes leading to a more or less obligatory mycoparasitism with limited growth and viability without the presence of the host. Hence, the *E. weberi* genome demonstrates a high degree of specialization, with a unique secretome containing an unusually high content of over 50% of proteins with unknown function. Further, the genome contains only 20% homologs with the closely related *T. atroviride, T. virens* and *T. reesei* and only 12% of the 1066 unique genes exhibit homology with proteins in the whole subdivision

**fungi**

of *Pezizomycotina* [15].

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.
