La diversité fongique des meules de plusieurs espèces de Macrotermitinae a été analysée au niveau taxinomique, fonctionnel et génétique à l’aide d’une approche polyphasique associant plusieurs techniques complémentaires. L’objectif étant d’évaluer la spécificité des taxons fongiques associés aux meules ainsi que les relations qu’ils entretiennent avec les termites champignonnistes. Une grande variété de phylotypes cultivables appartenant majoritairement au phylum des Ascomycètes a été obtenue par isolement et séquençage des ITS fongiques, et peu de séquences se sont révélées être spécifiques à un genre de Macrotermitinae particulier. Les profils physiologiques obtenus ont mis en évidence la nature saprophytique de la majorité des phylotypes et confirmé l’absence de taxons spécifiques. Par PCR-DGGE de l’ADN total de meules, 100% des phylotypes ITS et 28S fongiques identifiés étaient affiliés au genre Termitomyces. La technique Suicide Polymerase Endonuclease Restriction (SuPER) a été adaptée à la mycoflore des meules pour limiter l’impact de l’ADN majoritaire du Termitomyces symbiotique. Celle-ci a permis la détection de plusieurs autres populations fongiques. Les analyses phylogénétiques ont montré d’une part la spécificité des Xylaria associés aux meules de Macrotermitinae bien qu’aucune co-évolution n’ait été observée avec les termites hôtes et d’autre part leur affiliation dans un sous-genre spécifique. Une analyse préliminaire des facteurs d’inhibition a également révélé l’implication des termites dans la régulation des communautés fongiques des meules. Dans leur ensemble, nos résultats illustrent clairement l’influence des Macrotermitinae sur les communautés fongiques telluriques pendant leurs différentes activités. / Fungal diversity of several Macrotermitinae fungus combs was analyzed at taxonomic, functional and genetic levels using a polyphasic approach. The aim of this thesis was to evaluate the specificity of fungal strains from combs and to elucidate their relationship with fungus-growing termites. A large variety of culturable phylotypes mainly belonging to Ascomycota phylum was retrieved using conventional isolation techniques followed by sequencing of ITS1-5.8S-ITS2 region. Based on the obtained results, there is evidence for any speciesspecificity between these taxa and a given genus of Macrotermitinae. This finding was supported by the physiological profile of some representative phylotypes which revealed the saprophytic nature of most of the isolates. By PCR-DGGE analysis of fungal ITS and LSU, all of the sequences were belonged to Termitomyces genus. The Suicide Polymerase Endonuclease Restriction method was adapted to the analysis of comb mycoflora for restricting the impact of the dominant Termitomyces DNA. As expected, this latter technique revealed non-Termitomyces fungal populations. Phylogenetic analysis also showed the specificity of termiteassociated Xylaria although they do not evolved with termite hosts, and also their affiliation to a new genus or at least a specific sub-genus. Preliminary investigation revealed the implication of termite workers in fungal regulation in fungus combs. All in one, our results clearly underline the great impact of fungus-growing termite species on soil fungal community during their activities.

A diversidade de organismos oriundos do ambiente marinho constitui uma fonte significativa de substâncias estruturalmente inéditas e biologicamente ativas, dentre as quais, diversas inspiraram o desenvolvimento de novas classes de agentes terapêuticos. Neste contexto, macroalgas vermelhas do gênero Bostrychia (Rhodomelaceae) foram coletadas em praias do litoral norte do estado de São Paulo e têm sido objeto de estudos químicos e biológicos, no Laboratório de Química Orgânica do Ambiente Marinho (LQOAM - NPPNS) da FCFRPUSP, sob a supervisão da Profa. Dra. Hosana M. Debonsi. As algas da espécie Bostrychia radicans demonstraram potencial quando avaliadas as atividade citotóxica, tripanocida, leishmanicida e antimicrobiana; além de um perfil químico interessante, evidenciado pelo isolamento de substâncias inéditas na literatura. Neste contexto, o presente trabalho descreve a continuidade do estudo químico da espécie B. radicans, coletada no Manguezal do Rio Escuro, em Ubatuba-SP; bem como o potencial biológico desta espécie, além da avaliação da atividade de enzimas fenolsulfatases na espécie. Ainda, no sentido de explorar novas fontes promissoras para o isolamento de substâncias bioativas, este trabalho descreve o isolamento de micro-organismos endofíticos associados à espécie B. radicans. Foram isoladas 45 linhagens de micro-organismos; dentre as quais foram selecionadas nove linhagens para obtenção de extratos e realização de triagens química e biológica. A partir desta triagem inicial, foi realizado o estudo químico dos fungos Xylaria sp., Penicillium brevicompactum e Phomopsis longicolla. A partir da Xylaria sp. foram isoladas as seguintes substâncias: ácido 2,5-diidroxibenzóico, 8-diidroxinaftol 1-O-a-glucopiranosídeo, 8-metóxi-3-metil-1- isocromanona e ácido pilifórmico. O estudo químico de Penicillium brevicompactum resultou no isolamento das substâncias: ácido micofenólico, asperfenamato, brevianamida A, brevianamida C e brevianamida oxindol, substância inédita como produto natural. A partir de Phomopsis longicolla foi isolado o dicerandrol C. Este trabalho descreve ainda o potencial biológico de algumas destas substâncias isoladas. O estudo químico e biológico de microorganismos realizado no LQOAM estimulou a consolidação de uma colaboração com o Prof. Dr. Isidro C. Gonzalez, através da realização de um estágio de 12 meses no Laboratório Botrytis (Departamento de Química Orgânica, Universidade de Cádiz). Durante este período foi realizado o estudo químico do fitopatógeno Botrytis cinerea, visando o isolamento de novos metabólitos ou toxinas; além do estudo da biogênese destas substâncias, através de ensaios utilizando precursores isotopicamente marcados. / The diversity of organisms from the marine environment is a significant source of structurally novel and biologically active substances, several of which have inspired the development of new classes of therapeutic agents. In this context, red macroalgae belonging to Bostrychia genus (Rhodomelaceae) were collected on beaches of the north coast of São Paulo State and have been studied chemically and biologically in the Laboratory of Organic Chemistry of the Marine Environment - (LQOAM - NPPNS) at FCFRP-USP, under Prof. Hosana M. Debonsi supervision. Algae Bostrychia radicans species showed cytotoxic, trypanocidal, antileishmanial and antimicrobial potential, besides a interesting chemical profile, evidenced by the isolation of new compounds in the literature. In this context, this work describes the sequential chemical study of B. radicans species, collected at the Rio Escuro Mangrove, Ubatuba-SP, as well as the biological potential of this species. Also, the phenolsulphatases enzyme activity was evaluated in this species. Still, in order to explore new promising sources for the isolation of bioactive substances, this study describes the isolation of endophytic microorganisms associated to B. radicans. In this way, 45 strains of microorganisms were isolated and nine strains were selected for extracts preparation; and subsequently chemical and biological screenings. Based on the biological screening and chemical profile analyses, the large-scale fermentation of the endophytic fungi Xylaria sp., Penicillium brevicompactum and Phomopsis longicolla was carried out. The chromatographic purification of the bioactive acethyl acetate extract from Xylaria sp. allowed the isolation of 2,5-dihydroxybenzoic acid, 8- dihydroxynaphtol 1-O-a-glucopyranoside, 8-methoxy-3-methyl-1-isochromanone and piliformic acid. Chemical studies of Penicillium brevicompactum resulted in the isolation of: mycophenolic acid, asperphenamate, brevianamide A, brevianamide C and brevianamide oxindole, isolated for the first time as a natural product. From Phomopsis longicolla was isolated dicerandrol C. This thesis also describes the potential biological of some of these isolated compounds. The chemical and biological studies of microorganisms achieved in LQOAM encouraged the consolidation of a collaboration work with Prof. Dr. Isidro C. Gonzalez, through the completion of a 12-month internship at the Laboratory Botrytis (Department of Organic Chemistry, University of Cádiz). During this period, was conducted the chemical study of plant pathogen Botrytis cinerea, aiming the isolation of new metabolites or toxins, in addition to studying the biogenesis of these substances, through experiments using isotopically labeled precursors.

A diversidade de organismos oriundos do ambiente marinho constitui uma fonte significativa de substâncias estruturalmente inéditas e biologicamente ativas, dentre as quais, diversas inspiraram o desenvolvimento de novas classes de agentes terapêuticos. Neste contexto, macroalgas vermelhas do gênero Bostrychia (Rhodomelaceae) foram coletadas em praias do litoral norte do estado de São Paulo e têm sido objeto de estudos químicos e biológicos, no Laboratório de Química Orgânica do Ambiente Marinho (LQOAM - NPPNS) da FCFRPUSP, sob a supervisão da Profa. Dra. Hosana M. Debonsi. As algas da espécie Bostrychia radicans demonstraram potencial quando avaliadas as atividade citotóxica, tripanocida, leishmanicida e antimicrobiana; além de um perfil químico interessante, evidenciado pelo isolamento de substâncias inéditas na literatura. Neste contexto, o presente trabalho descreve a continuidade do estudo químico da espécie B. radicans, coletada no Manguezal do Rio Escuro, em Ubatuba-SP; bem como o potencial biológico desta espécie, além da avaliação da atividade de enzimas fenolsulfatases na espécie. Ainda, no sentido de explorar novas fontes promissoras para o isolamento de substâncias bioativas, este trabalho descreve o isolamento de micro-organismos endofíticos associados à espécie B. radicans. Foram isoladas 45 linhagens de micro-organismos; dentre as quais foram selecionadas nove linhagens para obtenção de extratos e realização de triagens química e biológica. A partir desta triagem inicial, foi realizado o estudo químico dos fungos Xylaria sp., Penicillium brevicompactum e Phomopsis longicolla. A partir da Xylaria sp. foram isoladas as seguintes substâncias: ácido 2,5-diidroxibenzóico, 8-diidroxinaftol 1-O-a-glucopiranosídeo, 8-metóxi-3-metil-1- isocromanona e ácido pilifórmico. O estudo químico de Penicillium brevicompactum resultou no isolamento das substâncias: ácido micofenólico, asperfenamato, brevianamida A, brevianamida C e brevianamida oxindol, substância inédita como produto natural. A partir de Phomopsis longicolla foi isolado o dicerandrol C. Este trabalho descreve ainda o potencial biológico de algumas destas substâncias isoladas. O estudo químico e biológico de microorganismos realizado no LQOAM estimulou a consolidação de uma colaboração com o Prof. Dr. Isidro C. Gonzalez, através da realização de um estágio de 12 meses no Laboratório Botrytis (Departamento de Química Orgânica, Universidade de Cádiz). Durante este período foi realizado o estudo químico do fitopatógeno Botrytis cinerea, visando o isolamento de novos metabólitos ou toxinas; além do estudo da biogênese destas substâncias, através de ensaios utilizando precursores isotopicamente marcados. / The diversity of organisms from the marine environment is a significant source of structurally novel and biologically active substances, several of which have inspired the development of new classes of therapeutic agents. In this context, red macroalgae belonging to Bostrychia genus (Rhodomelaceae) were collected on beaches of the north coast of São Paulo State and have been studied chemically and biologically in the Laboratory of Organic Chemistry of the Marine Environment - (LQOAM - NPPNS) at FCFRP-USP, under Prof. Hosana M. Debonsi supervision. Algae Bostrychia radicans species showed cytotoxic, trypanocidal, antileishmanial and antimicrobial potential, besides a interesting chemical profile, evidenced by the isolation of new compounds in the literature. In this context, this work describes the sequential chemical study of B. radicans species, collected at the Rio Escuro Mangrove, Ubatuba-SP, as well as the biological potential of this species. Also, the phenolsulphatases enzyme activity was evaluated in this species. Still, in order to explore new promising sources for the isolation of bioactive substances, this study describes the isolation of endophytic microorganisms associated to B. radicans. In this way, 45 strains of microorganisms were isolated and nine strains were selected for extracts preparation; and subsequently chemical and biological screenings. Based on the biological screening and chemical profile analyses, the large-scale fermentation of the endophytic fungi Xylaria sp., Penicillium brevicompactum and Phomopsis longicolla was carried out. The chromatographic purification of the bioactive acethyl acetate extract from Xylaria sp. allowed the isolation of 2,5-dihydroxybenzoic acid, 8- dihydroxynaphtol 1-O-a-glucopyranoside, 8-methoxy-3-methyl-1-isochromanone and piliformic acid. Chemical studies of Penicillium brevicompactum resulted in the isolation of: mycophenolic acid, asperphenamate, brevianamide A, brevianamide C and brevianamide oxindole, isolated for the first time as a natural product. From Phomopsis longicolla was isolated dicerandrol C. This thesis also describes the potential biological of some of these isolated compounds. The chemical and biological studies of microorganisms achieved in LQOAM encouraged the consolidation of a collaboration work with Prof. Dr. Isidro C. Gonzalez, through the completion of a 12-month internship at the Laboratory Botrytis (Department of Organic Chemistry, University of Cádiz). During this period, was conducted the chemical study of plant pathogen Botrytis cinerea, aiming the isolation of new metabolites or toxins, in addition to studying the biogenesis of these substances, through experiments using isotopically labeled precursors.

La diversité fongique des meules de plusieurs espèces de Macrotermitinae a été analysée au niveau taxinomique, fonctionnel et génétique à l'aide d'une approche polyphasique associant plusieurs techniques complémentaires. L'objectif étant d'évaluer la spécificité des taxons fongiques associés aux meules ainsi que les relations qu'ils entretiennent avec les termites champignonnistes. Une grande variété de phylotypes cultivables appartenant majoritairement au phylum des Ascomycètes a été obtenue par isolement et séquençage des ITS fongiques, et peu de séquences se sont révélées être spécifiques à un genre de Macrotermitinae particulier. Les profils physiologiques obtenus ont mis en évidence la nature saprophytique de la majorité des phylotypes et confirmé l'absence de taxons spécifiques. Par PCR-DGGE de l'ADN total de meules, 100% des phylotypes ITS et 28S fongiques identifiés étaient affiliés au genre Termitomyces. La technique Suicide Polymerase Endonuclease Restriction (SuPER) a été adaptée à la mycoflore des meules pour limiter l'impact de l'ADN majoritaire du Termitomyces symbiotique. Celle-ci a permis la détection de plusieurs autres populations fongiques. Les analyses phylogénétiques ont montré d'une part la spécificité des Xylaria associés aux meules de Macrotermitinae bien qu'aucune co-évolution n'ait été observée avec les termites hôtes et d'autre part leur affiliation dans un sous-genre spécifique. Une analyse préliminaire des facteurs d'inhibition a également révélé l'implication des termites dans la régulation des communautés fongiques des meules. Dans leur ensemble, nos résultats illustrent clairement l'influence des Macrotermitinae sur les communautés fongiques telluriques pendant leurs différentes activités.

A number of fungi produce spalted wood, which is characterized by accumulation of black pigment in fine demarcation lines, often accompanied by discoloration or staining on the wood fibers. Specific spalting fungi were identified by molecular analysis. From a total of 19 isolates and 140 clones studied, 11 fungal species were identified. The two Chlorociboria species from North America were investigated and their anamorphs were unambiguously identified for the first time. Fungal pigment formation under the influence of moisture content and pH variation was investigated in sugar maple, American beech and agar inoculated with spalting fungi. Maximum pigment production occurred at treatment with pH 4.5 for sugar maple and beech inoculated with Trametes versicolor. Xylaria polymorpha produced external pigmentation in beech treated with buffer at pH 5 and sugar maple at pH 4.5. Fungal pigmentation by Trametes versicolor and Xylaria polymorpha was stimulated at low moisture content in both wood species tested. Melanin production by Inonotus hispidus and Polyporus squamosus was stimulated above 22-28% and 34-38% moisture content in beech and in sugar maple respectively. Fomes fomentarius and Polyporus brumalis produced maximum pigmentation in beech at 26 - 41% and in sugar maple at 59 - 96% moisture content. The variation of the moisture content and pH values of wood substrates can stimulate the intensity of pigmentation of specific fungi in wood. To investigate melanin synthesis from a variety of melanin precursors, experimental research on three spalting fungi tested their reaction to catechol and L-Dopa melanin precursors in wood and agar substrate. The results indicate multiple biosynthesis pathways for melanin assembly in Trametes versicolor, Xylaria polymorha and Inonotus hispidus, and catechol produced most pigmentation in all spalting fungi investigated. Microscopic analysis by light, fluorescence, electron and confocal microscopy also indicates a bi- or multi-modal activity of melanin production and assembly by several spalting fungi. Possible variations of melanin assembly were identified based on fungal and wood species. Immunofluorescence and immunogold labelling with Mab 6D2 melanin antibody confirmed the melanin nature of the pigments produced by Oxyporus populinus, Trametes versicolor, Xylaria polymorpha, Fomes fomentarius, and Inonotus hispidus.

A number of fungi produce spalted wood, which is characterized by accumulation of black pigment in fine demarcation lines, often accompanied by discoloration or staining on the wood fibers. Specific spalting fungi were identified by molecular analysis. From a total of 19 isolates and 140 clones studied, 11 fungal species were identified. The two Chlorociboria species from North America were investigated and their anamorphs were unambiguously identified for the first time. Fungal pigment formation under the influence of moisture content and pH variation was investigated in sugar maple, American beech and agar inoculated with spalting fungi. Maximum pigment production occurred at treatment with pH 4.5 for sugar maple and beech inoculated with Trametes versicolor. Xylaria polymorpha produced external pigmentation in beech treated with buffer at pH 5 and sugar maple at pH 4.5. Fungal pigmentation by Trametes versicolor and Xylaria polymorpha was stimulated at low moisture content in both wood species tested. Melanin production by Inonotus hispidus and Polyporus squamosus was stimulated above 22-28% and 34-38% moisture content in beech and in sugar maple respectively. Fomes fomentarius and Polyporus brumalis produced maximum pigmentation in beech at 26 - 41% and in sugar maple at 59 - 96% moisture content. The variation of the moisture content and pH values of wood substrates can stimulate the intensity of pigmentation of specific fungi in wood. To investigate melanin synthesis from a variety of melanin precursors, experimental research on three spalting fungi tested their reaction to catechol and L-Dopa melanin precursors in wood and agar substrate. The results indicate multiple biosynthesis pathways for melanin assembly in Trametes versicolor, Xylaria polymorha and Inonotus hispidus, and catechol produced most pigmentation in all spalting fungi investigated. Microscopic analysis by light, fluorescence, electron and confocal microscopy also indicates a bi- or multi-modal activity of melanin production and assembly by several spalting fungi. Possible variations of melanin assembly were identified based on fungal and wood species. Immunofluorescence and immunogold labelling with Mab 6D2 melanin antibody confirmed the melanin nature of the pigments produced by Oxyporus populinus, Trametes versicolor, Xylaria polymorpha, Fomes fomentarius, and Inonotus hispidus.

Die vorliegende Dissertation befasst sich vor dem Hintergrund von pilzlicher Ökophysiologie und Umweltbiotechnologie mit der Isolierung, Reinigung und Charakterisierung von neuartigen Oxidoreduktasen aus kenianischen Pilzen (Eumycota). Unter Verwendung von selektiven, antibiotikahaltigen Agarmedien wurde 2016 eine Stammsammlung von 43 pilzlichen Isolaten angelegt, die Totholz, Laubstreu und Boden besiedelnde Arten umfasst und drei verschiedene kenianische Waldtypen und Biodiversitätsschwerpunkte berücksichtigt (ostafrikanische Regen-, Berg- und Küstenwälder). Die Isolate gehörten zu 21 Familien aus drei (Unter)stämmen: Basidiomycota, Ascomycota und Mucoromycotina. Unter ihnen befanden sich Weißfäulepilze und Streuzersetzer (aus den Familien Polyporaceae und Strophariceae), ein polyporaler Braunfäulepilz (Fomitopsis meliae) und zwei Vertreter der Familie Xylariaceae, die eine Moderfäule hervorrufen. Auf Grundlage morphologischer und molekularbiologischer Analysen konnte eine neue Art der Blätterpilz-Gattung Psathyrella identifiziert und als P. aberdarensis beschrieben werden. Extrazelluläre Aktivitäten von Unspezifischer Peroxygenase (UPO, EC 1.11.2.1) and DyP-Typ-Peroxidase (DyP, EC 1.11.1.19) wurden für einige der pilzlichen Isolate nachgewiesen, u.a. für P. aberdarensis (PabUPO) und den ascomycetalen Moderfäulepilz Xylaria grammica (XgrDyP). Die zugehörigen Enzymproteine wurden gereinigt und biochemisch characterisiert. Die PabUPOs werden in Form von drei verschiedenen Isoenzymen/Isoformen exprimiert und realisieren ungewöhnlich breite pH-Profile bei entsprechend hoher Enzymstabilität. Sie gehören zur Proteinfamilie der “langen” UPOs und katalysieren typische Peroxygenierungen, u.a. die Oxidation von Alkoholen, die Spaltung von Ethern, die Demethylenierung, die Oxygenierung aromatischer Ringe und – darüber hinaus – die Oxidation von Formylfurancarbonsäure zu Furandicarbonsäure (eine spezifische Reaktion, die für die Herstellung von biobasierten Polyestern aus nachwachsenden Rohstoffen von Bedeutung ist). Bei der XgrDyP handelt es sich um die erste Wildtyp-DyP eines Ascomyceten; sie ist in der Lage, Peroxidase-Substrate wie ABTS und 2,6-Dimethoxyphenol, aber auch den Anthrachinon-Farbstoff Reactive Blue 5, Veratrylalkohol, und – bemerkenswerterweise – Mangan (Mn2+) zu oxidieren, was auf neue physiologische Funktionen dieses Enzymtyps hinweist. Die Genome der beiden Enzymbildner wurden sequenziert und annotiert, was die Identifizierung der zugehörigen Enzyme-kodierenden Gene erlaubte. Neben den beiden exprimierten PabUPO-Genen wurden 46 weitere putative UPO-Sequencen im Psathyrella-Genom gefunden. Aufgrund des Fehlens ligninolytischer Klasse-II-Peroxidasen in den Genomen beider Pilze wird angenommen, dass die charakterisierten Hämperoxidasen von ökophysiologischer Bedeutung für alternative Wege des Abbaus von Lignozellulosen oder Humus sind. Auf Basis des gefundenen Kernbestands an lignocellulolytischen CAZy-Enzymen (d.h. Cellulasen, lytische Polysaccharid-Monooxygenasen, Laccase, H2O2-bildende Oxidasen), können P. aberdarensis and X. grammica den ökophysiologischen Gruppen der streuzersetzenden Weißfäulepilze bzw. holzbesiedelnden Moderfäulepilze zugerechnet werden.:TABLE OF CONTENTS LIST OF ABBREVIATIONS V ZUSAMMENFASSUNG VII SUMMARY IX MUHTASARI XI 1 INTRODUCTION 1 2 MATERIAL AND METHODS 35 3 RESULTS 54 4 DISCUSSION 105 5 CONCLUSION AND OUTLOOK 133 6 REFERENCES 137 7 APPENDIX 156 / The present dissertation deals, against the background of fungal eco-physiology and environmental biotechnology, with the isolation, purification and characterization of new fungal oxidoreducatses from Kenyan fungi (Eumycota). By using selective agar media supplemented with antibiotics, a culture collection comprising 43 fungal isolates dwelling in deadwood, leaf-litter and soil was established in 2016, considering three different Kenyan forest types and biodiversity hotspots (East African rainforest, mountain and coastal forests). The isolates turned out to belong to 21 families of the (sub)phyla Basidiomycota, Ascomycota and Mucoromycotina. Among them were white-rot and litter-decomposing fungi (from the families Polyporaceae and Strophariceae), a polyporous brown-rot species (Fomitopsis meliae) and two members of the family Xylariaceae causing soft-rot. By morphological and molecular analyses, a new species of the agaric genus Psathyrella was identified and described as Psathyrella aberdarensis. Extracellular activities of unspecific peroxygenase (UPO, EC 1.11.2.1) and DyP-type peroxidase (DyP, EC 1.11.1.19) were demonstrated for a few of the fungal isolates, among them P. aberdarensis (PabUPO) and the soft-rot ascomycete Xylaria grammica (XgrDyP), respectively. The corresponding enzyme proteins were purified and characterized. PabUPOs occur in form of three different isoenzymes/isoforms realizing unusually broad pH-profiles and stabilities. They belong to the clade of ‘long’ UPOs and catalyze typical peroxygenations, i.e. alcohol oxidation, ether cleavage, demethylenation, aromatic ring oxygenation, and beyond that, the oxidation of formylfuran carboxylic acid into furandicarboxylic acid (a specific reaction in the preparation of bio-based polyesters from renewable building blocks). XgrDyP is the first wild-type DyP reported for an ascomycetous fungus and was found to oxidize peroxidase substrates such as ABTS and 2,6-DMP but also Reactive Blue 5, veratryl alcohol and notably manganese (Mn2+), suggesting novel physiological functions of this enzyme type. The genomes of both producer species were sequenced and annotated, which allowed the identification of the corresponding enzyme-encoding genes. Besides the two expressed PabUPO genes, a further 46 putative UPO sequences were identified in the Psathyrella genome. Due to the absence of ligninolytic class II peroxidases in the genomes of both fungi, the characterized heme peroxidases may be of eco-physiological relevance for alternative pathways degrading lignocellulosic materials or humus. Based on the core set of lignocellulolytic CAZy enzymes (i.e. cellulases, lytic monosaccharide monooxygenases, laccase, H2O2-generating oxidases), P. aberdarensis and X. grammica can be classified within the eco-physiological groups of litter-decomposing white-rot and wood-colonizing soft-rot fungi, respectively.:TABLE OF CONTENTS LIST OF ABBREVIATIONS V ZUSAMMENFASSUNG VII SUMMARY IX MUHTASARI XI 1 INTRODUCTION 1 2 MATERIAL AND METHODS 35 3 RESULTS 54 4 DISCUSSION 105 5 CONCLUSION AND OUTLOOK 133 6 REFERENCES 137 7 APPENDIX 156

Alstonia scholaris is an evergreen tree native to Southeast Asia and Australia. It is commonly used as a medicinal plant throughout these regions. In the present study, an endophyte of the genus Xylaria was isolated from a stem of Alstonia scholaris, its mycelia and exudate extracted, and the extract assayed for growth inhibition of HeLa cancer cells in vitro. Several known compounds were isolated and identified based on NMR, infrared, and mass spectral data. The compounds identified are 19,20-epoxycytochalasin C; 19,20epoxycytochalasin D; and xylobovide. Two other compounds, fusaric acid and dehydrofusaric acid, were discovered in an endophyte of the Hypocreales family inhabiting the plant Acmena Graveolens.