10 Secondary Metabolites of Basidiomycetes 1 1 ANJA SCHU¨ FFLER ,TIMM ANKE CONTENTS c) Fomitella fraxinea (Polyporaceae) ..................... 219 I. Introduction ..................................... 210 d) Grifola frondosa II. Secondary Metabolites and Their Biological (Polyporaceae s. lat.) .............. 219 Activities ......................................... 210 e) Leucopaxillus gentianeus A. Terpenoids .................................. 211 (Tricholomataceae) ............... 219 1. Sesquiterpenoids ....................... 211 f) Clavariadelphus truncatus a) Resupinatus leightonii (Clavariaceae) ..................... 220 (Tricholomataceae) ............... 211 B. Polyketides, Fatty Acid Derivatives ........ 220 b) Conocybe siliginea a) Boreostereum vibrans (Bolbitiaceae) ...................... 212 (Stereaceae) ........................ 220 c) Ripartites tricholoma and b) Junghuhnia nitida R. metrodii (Paxillaceae) .......... 212 (Steccherinaceae) ................. 221 d) Omphalotus olearius, O. nidiformis c) Ceriporia subvermispora (Omphalotaceae) .................. 213 (Polyporaceae s. lat.) .............. 221 e) Radulomyces confluens d) Suillus luteus (Boletaceae) ........ 221 (Corticiaceae s. lat.) ............... 213 e) Hygrophorus spp. f) Gloeophyllum sp. (Hygrophoraceae) ................. 221 (Gloephyllaceae) ................... 214 f) Trametes menziesii g) Bovista sp. (Lycoperdaceae) ...... 214 (Polyporaceae s. lat.) .............. 221 h) Marasmius sp. g) Gerronema sp. (Tricholomataceae) ............... 214 (Tricholomataceae) ............... 222 i) Dichomitus squalens h) Imperfect Basidiomycete (Polyporaceae) ..................... 214 Strain 96244 ....................... 222 j) Macrocystidia cucumis i) Pterula sp. (Pterulaceae), (Tricholomataceae) ................ 214 Mycena spp. (Tricholomataceae) ... 222 k) Creolophus cirrhatus j) Terphenyls from Thelephora (Hericiaceae) ...................... 216 aurantiotincta, T. terrestris, l) Coprinus sp. (Coprinaceae) ....... 216 Hydnellum caeruleum, m) Dacrymyces sp. Sarcodon leucopus, S. scabrosus (Dacrymycetaceae) ............... 216 (all Thelephoraceae), and Paxillus n) Limacella illinita curtisii (Paxillaceae) ............... 222 (Amanitaceae) ..................... 217 C. Compounds of Unclear Biogenetic o) Boletus calopus (Boletaceae) ..... 217 Origin ........................................ 223 p) Russula lepida (Russulaceae) .... 217 a) Tremella aurantialba 2. Diterpenoids ............................ 217 (Tremellaceae) ..................... 223 a) Sarcodon scabrosus b) Stereum hirsutum (Stereaceae) .... 223 (Thelephoraceae) .................. 217 c) Antrodia serialis (Polyporaceae b) Mycena tintinnabulum s. lat.) ............................... 224 (Tricholomataceae) ............... 217 d) Aporpium caryae 3. Triterpenoids ........................... 218 (Tremellaceae) .................... 224 a) Irpex sp. (Steccherinaceae) ....... 218 e) Bondarzewia montana b) Favolaschia spp. (Bondarzewiaceae) ................ 224 (Favolaschiaceae) ................. 218 f) Cortinarius sp. (Cortinariaceae) ... 224 g) Chamonixia pachydermis (Boletaceae) ........................ 224 h) Serpula himantoides (Coniophoraceae) ................. 225 1 Institut fu¨r Biotechnologie und Wirkstoff-Forschung e.V./Institute i) Pholiota spumosa for Biotechnology and Drug Research, Erwin-Schroedinger-Strasse (Strophariaceae) ................... 225 56, 67663 Kaiserslautern, Germany; e-mail: [email protected] Physiology and Genetics, 1st Edition The Mycota XV T. Anke and D. Weber (Eds.) © Springer‐Verlag Berlin Heidelberg 2009 210 Anja Schu¨ffler and Timm Anke D. Amino Acid Derivatives .................... 225 entities among the metabolites of actinomycetes a) Aporpium caryae and other bacterial sources. This was furthered by (Tremellaceae) ..................... 226 the recent progress in cultivation techniques and III. Conclusions ...................................... 226 the development of fast methods for the isolation References ........................................ 226 and structural determination of natural com- pounds. The following chapter mainly deals with compounds described from 1998 on and focuses on biologically active metabolites. Some classes of I. Introduction fungal metabolites which presently are used as medical, veterinary, or agricultural antibiotics Basidiomycetes, a major class of higher fungi were dealt with in the chapter “Non-b-Lactam adapted to many different climates, habitats, and Antibiotics” of The Mycota, Vol. X (2002). For substrates have developed a rich and very diverse earlier reviews on bioactive natural products of secondary metabolism. Its products differ in bio- basidiomycetes and bioactive sesquiterpenes of genetic origin and structure remarkably from the fungi the reader is referred to Lorenzen and metabolites of ascomycetes or other prolific pro- Anke (1998), Abraham (2001), and Liu (2005). ducers of secondary metabolites like actinomy- cetes or myxobacteria. There are, however, some similarities to the products of plants, especially with regard to some polyketides, acetylenes, and II. Secondary Metabolites and Their sesquiterpenoids. The first systematic investiga- Biological Activities tions of basidiomycete metabolites originated after the discovery and introduction into clinical Basidiomycetes like other saprophytic or soil-inha- practise of penicillin, the first antibiotic not biting microorganisms are prolific producers of derived by chemical synthesis. Its great success secondary metabolites. Their mycelia and fruiting initiated a real “gold rush” in the search for new bodies are exposed to a number of predators or antibiotics and prospective producers. From 1940 competitors, which in some cases can explain the until the early 1950s mycelial cultures or fruiting production of antibiotics, insecticides, or feeding bodies of more than 2000 basidiomycetes were deterrents. Among the antibiotics the a-methylene screened for the production of antibiotics by the lactones and ketones have a very broad and unspe- pioneering groups of M. Anchel, A. Hervey, F. cific action against prokaryots and eukaryots while Kavanagh, W. J. Robbins, and W. H. Wilkins (for others are highly selective with regard to their reviews, see Florey et al. 1949; Wilkins and Harris biochemical targets and organisms. As demon- 1944). Their investigations resulted in the discov- strated for the producers of antifungal strobilurins, ery of pleuromutilin, the lead compound for the antibiotic production can be stimulated severalfold semisynthetic tiamulin used in veterinary practise in the presence of other, possibly competing, fungi and recently also in humans (Kavanagh et al. 1951; (Kettering et al. 2004). In many cases, however, a Ho¨genauer 1979; Daum et al. 2007). This system- possible benefit for the producing fungus is not atic search came to an end after Waksman’s dicov- obvious. This is especially true for secondary meta- ery of the streptomycetes as the most prolific bolites for which up to now no antibiotic or other producers of antibiotic metabolites. These soil biological activities have been detected. According bacteria are easily obtained and can be grown in to Za¨hner et al. (1983) these could be part of a simple media in large fermenters which greatly still ongoing “evolutionary playground” providing facilitates the discovery and production process. new chemical solutions for an improved fitness of Meanwhile the basidiomycetes and mainly their the producing organisms. This contribution covers fruiting bodies attracted the interest of natural metabolites derived from basidiomycetes and their products chemists as a source of toxins (Bresinsky biological activities published from 1998 until and Besl 1985), hallucinogens (Schultes and Hof- 2008. The compounds are arranged by their pre- mann 1980), and pigments (Gill and Steglich 1987; sumed biogenetic origin and the producing fungi. Gill 1999). A systematic screening of mycelial cul- Synthetic approaches are included when they have tures only regained interest when it became in- contributed to elucidate the (absolute) configura- creasingly difficult to discover new chemical tion or structure–activity studies. Secondary Metabolites of Basidiomycetes 211 A. Terpenoids isolated in different screenings because of their unusually high antibiotic and cytotoxic activities. Terpenoids are among the prominent metabolites These are often due to a high chemical reactivity of basidiomycetes. Most of these have structures which, however, makes these compounds less de- not encountered elsewhere in nature, with the sirable as possible lead structures. notable exception that some sesquiterpenes have ring structures also found in higher plants, e.g. caryophyllanes and acoranes (Lorenzen and Anke a) Resupinatus leightonii (Tricholomataceae) 1998; Abraham 2001). Geosmin (Fig. 10.1), with its 1(10),4-Germacradiene-2,6,12-triol, a new germa- characteristic musty-earthy odor and first de- crane sesquiterpene, and 1,6-farnesadiene-3,10, scribed as a typical streptomycete metabolite, 11-triol, a known nerolidol derivative, were isolated has now been identified as responsible for the from submerged cultures of Resupinatus leightonii. characteristic odor of Cortinarius herculeus (Cor- Both compounds (Fig. 10.1) inhibited the cAMP- tinariaceae), Cystoderma amianthinum (Agarica- induced appressorium formation in Magnaporthe ceae), and Cy. carcharias (Breheret et al. 1999). grisea and showed cytotoxic activity. The forma- tion of melanized appressoria is a