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Lichens—a promising source of bioactive secondary metabolites

Published online by Cambridge University Press:  12 February 2007

Joël Boustie  and
Martin Grube
Joël Boustie*
Affiliation:
Institut de Chimie de Rennes, Equipe: Substances Lichéniques et Photoprotection, UFR Pharmacie, 2 av du Pr. Léon Bernard (CS 34317), 35043 Rennes Cédex, France
Martin Grube
Affiliation:
Institute of Plant Sciences, Karl-Franzens-University Graz, Holteigasse 6, 8010 Graz, Austria
*
*Corresponding author: E-mail: [email protected]
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Abstract

Lichen-forming fungi are unique organisms, producing biologically active metabolites with a great variety of effects, including antibiotic, antimycobacterial, antiviral, anti-inflammatory, analgesic, antipyretic, antiproliferative and cytotoxic activities. However, only very limited numbers of lichen substances have been screened for their biological activities and their therapeutic potential in medicine. This is certainly due to the difficulties encountered in identification of the species, collection of bulk quantities, and the isolation of pure substances for structure determination and testing activity. Recently, possibilities for bypassing some of these former difficulties have arisen by the introduction of new techniques. This includes axenic cultivation for production of the genuine compounds or new ones, extraction of focused compounds, or synthesis of natural products or their derivatives for testing. Utilizing these new opportunities, the discovery of novel active metabolites, which could serve as lead compounds, is significantly facilitated. At the same time, the evolution of secondary metabolite patterns is studied using phylogenetic approaches. Yet, the genetic background of the complex chemical patterns is poorly understood. The scattered occurrence of some compounds suggests that their production evolved either in parallel or that ancient biosynthetic pathways are abandoned in many lineages. At least, studies on polyketide synthase genes from different lichen groups suggest a high level of gene paralogy. In this context, clades of orthologous polyketide synthase genes, which are often shared with distantly related non-lichenized fungi, can roughly be identified by their sequence similarity and their similar patterns of substitution rates. The functional assignment of paralogs is nevertheless difficult and reasonable only in a few cases. A global approach of the lichen metabolomic features appears to be essential in developing new and viable biotechnological processes which could afford suitable amounts of unique lichen compounds.

Keywords

bioactivitybiosynthesisdrugslichensmetabolites, phylogenyphytochemistry
Type
Research Article
Information
Plant Genetic Resources , Volume 3 , Issue 2 , August 2005 , pp. 273 - 287
Copyright
Copyright © NIAB 2005

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References

Ahmadjian, V and Reynolds, JT (1961) Production of biologically active compounds by isolated lichenized fungi. Science 133: 700–701.CrossRefGoogle ScholarPubMed
Amano, T, Miyagawa, H, Ueno, T and Hamada, N (2000) Production of 5,7-dihydroxy-6-hydroxymethyl-2-methoxy-1,4-naphthoquinone by the cultured lichen mycobiont of Opegrapha sp. no. 9771836. Zeitschrift für Naturforschung 55: 667–669.CrossRefGoogle Scholar
Asahina, Y (1936) Microchemischer Nachweis der Flechtenstoffe. I. Journal of Japanese Botany 12: 516–525.Google Scholar
BeGora, MD and Fahselt, D (2000) An alternative method for the quantification of lichen secondary products. The Bryologist 103: 563–567.CrossRefGoogle Scholar
BeGora, MD and Fahselt, D (2001) Usnic acid and atranorin concentrations in lichens in relation to bands of UV irradiance. The Bryologist 104: 134–140.CrossRefGoogle Scholar
Behera, BC and Makhija, U (2002) Inhibition of tyrosinase and xanthine oxidase by lichen species Bulbothrix setschwanensis. Current Science 82: 61–66.Google Scholar
Behera, BC, Adawwadkar, B and Makhija, U (2004) Capacity of some Graphidaceous lichens to scavenge superoxide and inhibition of tyrosinase and xanthine oxidase activities. Research Communications 87: 83–87.Google Scholar
Bézivin, C, Tomasi, S, Lohézic-Le, Devehat F and Boustie, J (2003) Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine 10: 499–503.CrossRefGoogle ScholarPubMed
Bézivin, C, Tomasi, S, Rouaud, I, Delcros, JG and Boustie, J (2004) Cytotoxic activity of compounds from the lichen: Cladonia convoluta. Planta Medica 70: 874–877.CrossRefGoogle ScholarPubMed
Bingle, LEH, Simpson, TJ and Lazarus, CM (1999) Ketosynthese domain probes identify two subclasses of fungal polyketide synthese genes. Fungal Genetics and Biology 26: 209–223.CrossRefGoogle Scholar
Bjerke, JW, Lerfall, K and Elvebakk, A (2002) Effects of ultraviolet radiation and PAR on the content of usnic and divaricatic acids in two arctic-alpine lichens. Photochemical and Photobiological Sciences 1: 678–685.CrossRefGoogle ScholarPubMed
Bjerke, JW, Zielke, M and Solheim, B (2003) Long-term impacts of simulated climatic change on secondary metabolism, thallus structure and nitrogen fixation activity in two cyanolichens from the Arctic. New Phytologist 159: 361–367.CrossRefGoogle ScholarPubMed
Blanch, M, Blanco, Y, Fontaniella, B, Legaz, ME and Vicente, C (2001) Production of phenolics by immobilized cells of the lichen Pseudevernia furfuracea: the role of epiphytic bacteria. International Microbiology 4: 89–92.CrossRefGoogle ScholarPubMed
Blanco, Y, Blanch, M, Fontaniella, B, Legaz, ME, Millanes, AM, Pereira, EC and Vicente, C (2002) Bioproduction of lichen phenolics by immobilized cells with emphasis on the role of epiphytic bacteria. Journal of the Hattori Botanical Laboratory 92: 245–260.Google Scholar
Brij, Lal (1988) Traditional remedies for bone fracture among the tribals of Madhya Pradesh, India. Aryavaidyan 1: 190–195.Google Scholar
Brij, Lal and Upreti, DK (1995) Ethnobotanical notes on three Indian lichens. Lichenologist 27: 77–79.Google Scholar
Brij, Lal, Upreti, DK and Kalakoti, BS (1985) Ethnobotanical utilization of lichens by the tribals of Madhya Pradesh. Journal of Economic and Taxonomic Botany 7: 203–204.Google Scholar
Buffoni Hall, RS, Bornman, JF, Björn, LO (2002) UV-induced changes in pigment content and light penetration in the fruticose lichen Cladonia arbuscula ssp. mitis. Journal of Photochemistry and Photobiology B (Biology) 66: 13–20.CrossRefGoogle ScholarPubMed
Cain, BF (1961) Potential antitumour agents. Part I. Polyporic acid series. Journal of the Chemical Society Abstracts 936–940.CrossRefGoogle Scholar
Cain, BF (1966) Potential anti-tumour agents. Part IV. Polyporic acid series. Journal of the Chemical Society 1041–1045.Google Scholar
Cardarelli, M, Serino, G, Campanella, L, De Ercole, P, Cicco Nardone, F, Alesiani, O and Rossiello, F (1997) Antimitotic effects of usnic acid on different biological systems. Cellular and Molecular Life Sciences 53: 667–672.CrossRefGoogle ScholarPubMed
Correché, ER, Carrasco, M, Giannini, F, Piovano, M, Garbarino, J and Enriz, D (2002) Cytotoxic screening activity of secondary lichen metabolites. Acta Farmaceutica Bonaerense 21: 273–278.Google Scholar
Correché, ER, Enriz, RD, Piovano, M, Garbarino, J, Gomez-Lechon, MJ (2004) Cytotoxic and apoptotic effects on hepatocytes of secondary metabolites obtained from lichens. Alternatives to Laboratory Animals 32: 605–615.CrossRefGoogle ScholarPubMed
Correia, Da and Silva, J (1981) Acçao anestésica local de produtos extraidos de liquens. Revista Portuguesa Farmacia 31: 69–72.Google Scholar
Cox, PA, Banack, SA, Murch, SJ, Rasmussen, U, Tien, G, Bidigare, RR, Metcalf, JS, Morrison, LF, Codd, GA and Bergman, B (2005) Diverse taxa of cyanobacteria produce β- N -methylamino- l -alanine, a neurotoxic amino acid. Proceedings of the National Academy of Sciences, USA 102: 5074–5078.CrossRefGoogle ScholarPubMed
Culberson, CF (1969) Chemical and Botanical Guide to Lichen Products, Durham: University of North Carolina.Google Scholar
Culberson, CF (1970) Supplement to ‘Chemical and Botanical Guide to Lichen Products’. The Bryologist 73: 177–377.CrossRefGoogle Scholar
Culberson, CF (1972) Improved conditions and new data for the identification of lichen products by a standardized thin-layer chromatographic method. Journal of Chromatography 72: 113–125.CrossRefGoogle ScholarPubMed
Culberson, CF and Armaleo, D (1992) Induction of a complete secondary-product pathway in cultures of a lichen fungus. Experimental Mycology 16: 52–63.CrossRefGoogle Scholar
Culberson, CF and Kristinsson, H (1970) A standardized method for the identification of lichen products. Journal of Chromatography 46: 85–93.CrossRefGoogle Scholar
Culberson, CF, Culberson, WL and Johnson, A (1977) Second Supplement to ‘Chemical and Botanical Guide to Lichen Products’ Missouri Botanical Garden St. Louis: American Bryological and Lichenologial SocietyCrossRefGoogle Scholar
De Angelis, F, Ceci, R, Quaresima, R, Reale, S Di and Tullio, A (2003) Investigation by solid phase microextraction and gas chromatography/mass spectrometry of secondary metabolites in lichens deposited on stone monuments. Rapid Communication in Mass Spectrometry 17: 526–531.CrossRefGoogle ScholarPubMed
Demleitner, S, Kraus, J and Franz, G (1991) Synthese und Antitumoraktivitat von Licheninderivaten. Pharmazie in unserer Zeit 20: 120Google Scholar
DePriest, PT (1994) Variation in the Cladonia chlorophaea complex II: ribosomal DNA variation in a Southern Appalachian population. The Bryologist 97: 117–126.CrossRefGoogle Scholar
Durazo, FA, Lassman, C, Han, SHB, Saab, S, Lee, NP, Kawano, M, Saggi, B, Gordon, S, Farmer, DG, Yersiz, H, Goldstein, RLI, Ghobrial, M and Busuttil, RW (2004) Fulminant liver failure due to usnic acid for weight loss. American Journal of Gastroenterology 99: 950–952.Google Scholar
Edwards, HGM, Newton, EM, Wynn-Williams, DD, Lewis-Smith, RI (2003) Non-destructive analysis of pigments and other organic compounds in lichens using Fourier-transform Raman spectroscopy: a study of Antartic epilithic lichens. Spectrochimica Acta Part A 59: 2301–2309.CrossRefGoogle Scholar
Ejiri, H, Sankawa, U and Shibata, S (1975) Graciliformin and its acetates in Cladonia graciliformis. Phytochemistry 14: 277–279.Google Scholar
Ernst-Russell, MA, Chai, CLL, Hurne, AM, Waring, P, Hockless, DCR and Elix, JA (1999 a) Revision and cytotoxic activity of the scabrosin esters, epidithiopiperazinediones from the lichen Xanthoparmelia scabrosa. Australian Journal of Chemistry 52: 279–283.CrossRefGoogle Scholar
Ernst-Russell, MA, Elix, JA, Chai, CLL, Willis, AC, Hamada, N and Nash, TH (1999 b) Hybocarpone, a novel cytotoxic naphthazarin derivative from mycobiont cultures of the lichen Lecanora hybocarpa. Tetrahedron Letters 40: 6321–6324.CrossRefGoogle Scholar
Esimone, CO, Adikwu, MU, Ebi, GC, Anaga, A and Njoku, C (1999) Preliminary physicochemical evaluations and bioactive properties of column fractions from the lichen. Bollettino Chimico Farmaceutico 138: 169–175.Google ScholarPubMed
European Pharmacopeia (2005) Iceland moss—Lichen islandicus. European Pharmacopeia, 5th edn (Vol. 5). Strasbourg: Council of Europe.Google Scholar
Feige, GB, Lumbsch, HT, Huneck, S and Elix, JA (1993) The identification of lichen products by a standardized high-performance liquid chromatographic method. Journal of Chromatography 646: 417–427.CrossRefGoogle Scholar
Fontaniella, B, Legaz, ME, Pereira, EC, Sebastian, B and Vicente, C (2000) Requirements to produce fumarprotocetraric acid using alginate-immobilized cells of Cladonia verticillaris. Biotechnology Letters 22: 813–817.CrossRefGoogle Scholar
Fox, CH and Huneck, S (1969) The formation of roccellic acid, eugenitol, eugenetin, and rupicolon by the mycobiont Lecanora rupicola. Phytochemistry 8: 1301–1304.CrossRefGoogle Scholar
Gauslaa, Y and McEvoy, M (2005) Seasonal variation in solar radiation drive acclimation of the sun-screening compound parietin in the lichen Xanthoria parietina. Basic and Applied Ecology 6: 75–82.CrossRefGoogle Scholar
Ghione, M, Parrello, D and Grasso, L (1988) Usnic acid revisited, its activity on oral flora. Chemiotherapia 7: 302–305.Google ScholarPubMed
Grube, M and Blaha, J (2003) On the phylogeny of some polyketide synthase genes in the lichenized genus Lecanora. Mycological Research 107: 1419–1426.CrossRefGoogle ScholarPubMed
Hamada, N (1988) Depside from isolated lichen mycobiont II. Lichenologist 10: 294–295.CrossRefGoogle Scholar
Hamada, N (1989) The effect of various culture conditions on depside production by an isolated mycobiont. The Bryologist 92: 310–313.Google Scholar
Hamada, N (1993) Effects of osmotic culture conditions on cultured mycobionts. The Bryologist 96: 569–572.CrossRefGoogle Scholar
Hamada, N and Ueno, T (1987) Depside from an isolated lichen mycobiont. Agricultural and Biological Chemistry 51: 1705–1706.Google Scholar
Hawksworth, DL (2003) Hallucinogenic and toxic lichens. International Lichenological Newsletter 36: 33–35.Google Scholar
Hidalgo, ME, Fernandez, E, Quilhot, W and Lissi, EA (1993) Photohaemolytic activity of lichen metabolites. Journal of Photochemistry and Photobiology B 21: 37–40.Google Scholar
Hidalgo, ME, Fernandez, E, Quilhot, W and Lissi, E (1994) Antioxidant activity of depsides and depsidones. Phytochemistry 37: 1585–1587.CrossRefGoogle ScholarPubMed
Higuchi, M, Miura, Y, Boohene, J, Kinoshita, Y, Yamamoto, Y, Yoshimura, I and Yamada, Y (1993) Inhibition of tyrosinase activity by cultured lichen tissues and bionts. Planta Medica 59: 253–255.Google Scholar
Hirabayashi, K, Iwata, S, Ito, M, Shigeta, S, Narui, T, Mori, T and Shibata, S (1989) Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro. Chemical and Pharmaceutical Bulletin 37: 2410–2412.Google Scholar
Hirayama, T, Fujikawa, F, Kasahara, T, Otsuka, M, Nishida, N and Mizuno, D (1980) Anti-tumor activities of some lichen products and their degradation products. Yakugaku Zasshi 100: 755–759.CrossRefGoogle ScholarPubMed
Huelsenbeck, JP and Ronquist, F (2001) MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 17: 754–755.CrossRefGoogle ScholarPubMed
Huneck, S (1999) The significance of lichens and their metabolites. Naturwissenschaften 86: 559–570.CrossRefGoogle ScholarPubMed
Huneck, S (2001) Progress in the Chemistry of Organic Natural Products, Vol. 81. New Results on the Chemistry of Lichen Substances. New York: Springer.Google Scholar
Huneck, S and Himmelreich, U (1995) Arthogalin, a cyclic depsipeptide from the lichen Arthothelium galapagoense. Zeitschrift für Naturforschung, B: Chemical Sciences 50: 1101–1103.CrossRefGoogle Scholar
Huneck, S and Yoshimura, I (1996) Identification of Lichen Substances, Berlin: Springer.Google Scholar
Huneck, S, Porzel, A and Schmidt, J (1993) Structure and synthesis of arthonin, a lichen metabolite from Arthonia endlicheri. Tetrahedron: Asymmetry 4: 303–311.Google Scholar
Huneck, S, Lumbsch, HT, Porzel, A and Schmidt, J (2004) Die Verteilung von Flechteninhaltsstoffen in Lecanora muralis und Lecidea inops und die Abhängigkeit der Usninsäure-Konzentration vom Substrat und von den Jahreszeiten bei Lecanora muralis. Bibliotheca Lichenologica 88: 211–221.Google Scholar
Huovinen, K (1987) A standard HPLC method for the analysis of aromatic lichen in Progress and Problems in Lichenology in the Eighties. Bibliotheca Lichenologica 25: 457–466.Google Scholar
Huovinen, K and Lampero, M (1989) Usnic acid as a mitotic inhibitor in the allium test. Planta Medica 55: 98Google Scholar
Huovinen, K, Hiltunen, R, Von Schahtz, M (1985) A high performance liquid chromatographic method for the analysis of lichen compounds from the genera Cladina and Cladonia. Acta Pharmaceutica Fennica 94: 99–112.Google Scholar
Ihlen, PG and Ekman, S (2002) Outline of phylogeny and character evolution in Rhizocarpon (Rhizocarpaceae, lichenized Ascomycota) based on nuclear ITS and mitochondrial SSU ribosomal DNA sequences. Biological Journal of the Linnean Society 77: 535–546.Google Scholar
Ingólfsdóttir, K (2002) Molecules of interest: usnic acid. Phytochemistry 61: 729–736.CrossRefGoogle Scholar
Ingólfsdóttir, K, Bloomfield, SF and Hylands, PJ (1985) In vitro evaluation of the antimicrobial activity of lichen metabolites as potential preservatives. Antimicrobial Agents and Chemotherapy 28: 289–292.CrossRefGoogle ScholarPubMed
Ingólfsdóttir, K, Breu, W, Huneck, S, Gudjonsdottir, GA and Wagner, H (1994) In vitro inhibition of 5-lipoxygenase by protolichesterinic acid from Cetraria islandica. Phytomedicine 1: 187–191.Google Scholar
Ingólfsdóttir, K, Hjálmarsdóttir, MÁ, Guðjónsdóttir, GA, Brynjolfsdóttir, A, Sigurðsson, A, Steingrímsson, Ó (1997) In vitro susceptibility of Helicobacter pylori to protolichesterinic acid from Cetraria islandica. Antimicrobial Agents and Chemotherapy 41: 215–217.CrossRefGoogle ScholarPubMed
Ingólfsdóttir, K, Lee, SK, Bhat, KPL, Lee, K, Chai, HB, Kristinsson, H, Song, LL, Gills, J, Gudmundsdottir, JT, Mata-Greenwood, E, Jang, MS and Pezzuto, JM (2000) Evaluation of selected lichens from Iceland for cancer chemopreventive and cytotoxic activity. Pharmaceutical Biology 38: 313–317.CrossRefGoogle ScholarPubMed
Ingólfsdóttir, K, Gudmundsdóttir, GF, Ogmundsdóttir, HM, Paulus, K, Haraldsdóttir, K, Kristinsson, H and Bauer, R (2002) Effect of tenuiorin and metyl orsellinate from the lichen Peltigera leucophebia on 5-/15-lipoxygenases and proliferation of malignant cell lines in vitro. Phytomedicine 9: 654–658.Google Scholar
Jayaprakasha, GK and Rao, LJ (2000) Phenolic constituents from the lichen Parmotrema stuppeum (Nyl.) Hale and their antioxidant activities. Zeitschrift für Naturforschung 55: 1018–1022.CrossRefGoogle Scholar
Keller, NP and Hohn, TM (1997) Metabolic pathway gene clusters in filamentous fungi. Fungal Genetics and Biology 21: 17–21.CrossRefGoogle ScholarPubMed
Kinoshita, Y, Yamamoto, Y, Yoshimura, I, Kurokawa, T and Yamada, Y (1993) Production of usnic acid in cultured Usnea hirta. Bibliotheca Lichenologica 53: 137–146.Google Scholar
Kinoshita, K, Saito, D, Koyama, K, Takahashi, K, Sato, Y, Okuyama, E, Fujimoto, H and Yamazaki, M (2002) Monoamino oxidase inhibitory effects of some lichen compounds and their synthetic analogues. Journal of the Hattori Botanical Laboratory 92: 277–284.Google Scholar
Kon, Y, Iwashina, T, Kashiwadani, H, Wardlaw, JD and Elix, J (1997) A new dibenzofuran, isostrepsilic acid, produced by cultured mycobiont of the lichenized ascomycete Usnea orientalis. Journal of Japanese Botany 72: 67–71.Google Scholar
Kristmundsdóttir, T, Aradóttir, HA, Ingólfsdóttir, KOgmunsdóttir, HM (2002) Solubilization of the lichen metabolite (+)-usnic acid for testing in tissue culture. Journal of Pharmacy and Pharmacology 54: 1447–1452.Google Scholar
Kroken, S, Glass, NL, Taylor, JW, Yoder, OC and Turgeon, BG (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proceedings of the National Academy of Sciences, USA 100: 15670–15675.Google Scholar
Kumar, K and Upreti, DK (2001) Parmelia spp. (lichen)—in ancient medicinal plant lore of India. Economic Botany 55: 458–459.Google Scholar
Kumar, S and Muller, K (1999) Lichen metabolites. I. Inhibitory action against leukotriene B4 biosynthesis by a non-redox mechanism. Journal of Natural Products 62: 817–820.CrossRefGoogle ScholarPubMed
Kupchan, SM and Kopperman, HL (1975) l -Usnic acid: tumor inhibitor isolated from lichens. Experientia 31: 625Google Scholar
Lauterwein, M, Oethinger, M, Belsner, K, Peters, T and Marre, R (1995) In vitro activities of the lichen secondary metabolites vulpinic acid, (+)-usnic acid and (?)-usnic acid against aerobic and anaerobic microorganisms. Antimicrobial Agents and Chemotherapy 39: 2541–2543.CrossRefGoogle ScholarPubMed
Lawrey, JD (1986) Biological role of lichen substances. The Bryologist 89: 11–122.Google Scholar
Lawrey, JD (1995) The chemical ecology of lichen mycoparasites. Canadian Journal of Botany 73: (Suppl. 1) 603–608.Google Scholar
Lee, T, Yun, S-H, Hodge, KT, Humber, RA, Krasnoff, SB, Turgeon, GB, Yoder, OC and Gibson, DM (2001) Polyketide synthase genes in insect- and nematode-associated fungi. Applied Microbiology and Biotechnology 56: 181–187.Google Scholar
Legaz, ME and Vicente, C (1983) Endogenous inactivators of arginase, l-arginine decarboxylase and agmatine amidinohydrolase in Evernia prunastri thallus. Plant Physiology 71: 300–302.CrossRefGoogle ScholarPubMed
Legaz, ME, Vicente, C and Pedrosa, MM (2001) Binding of lichen phenolics to purified secreted arginase from the lichen Evernia prunastri. Journal of Biochemistry and Molecular Biology 34: 194–200.Google Scholar
Leuckert, C and Poelt, J (1978) Über Nord-Süd-Gradienten von Chemotypen europäischer Flechten. Plant Systematics and Evolution 130: 53–77.Google Scholar
Leuckert, C, Ahmadjian, V, Culberson, CF and Johnson, A (1990) Xanthones and depsidones of the lichen Lecanora dispersa in nature and of its mycobiont in culture. Mycologia 82: 370–378.CrossRefGoogle Scholar
Lisickov, K, Najdenova, V and Zoltan, D (2002) Application of supercritical CO 2 extraction for separation of natural antibiotics from lichens. Herba Polonica 48: 32–39.Google Scholar
Lutzoni, F, Pagel, M and Reeb, V (2001) Major fungal lineages are derived from lichen symbiotic ancestors. Nature 411: 937–940.Google Scholar
Lutzoni, F, Kauff, F, Cox, CJ, McLaughlin, D, Celio, G, Dentinger, B, Padamsee, M, Hibbett, D, James, TY, Baloch, E, Grube, M, Reeb, V, Hofstetter, V, Schoch, C, Arnold, AE, Miadlikowska, J, Spatafora, J, Johnson, D, Hambleton, S, Crockett, M, Shoemaker, R, Sung, G-H, Lücking, R, Lumbsch, T, O'Donnell, K, Binder, M, Diederich, P, Ertz, D, Gueidan, C, Hall, B, Hansen, K, Harris, RC, Hosaka, K, Lim, Y-W, Liu, Y, Matheny, B, Nishida, H, Pfister, D, Rogers, J, Rossman, A, Schmitt, I, Sipman, H, Stone, J, Sugiyama, J, Yahr, R and Vilgalys, R (2004) Assembling the fungal tree of life: progress, classification, and evolution of subcellular traits. American Journal of Botany 91: 1446–1480.Google Scholar
MacGillivray, T and Helleur, R (2001) Analysis of lichens under environmental stress using TMAH thermochemolysis-gas chromatography. Journal of Analytical and Applied Pyrolysis 58/59, 465–480.Google Scholar
Matsubara, H, Kinoshita, K, Koyama, K, Ye, Y, Takahashi, K, Yoshimura, I, Yamamoto, Y, Miura, Y and Kinoshita, Y (1997) Anti-tyrosinase activity of lichen metabolites and their synthetic analogues. Journal of the Hattori Botanical Laboratory 83: 179–185.Google Scholar
Matsubara, H, Miharu, K, Kinoshita, K, Koyama, K, Ye, Y, Takahashi, K, Yoshimura, I, Yamamoto, Y, Miura, Y and Kinoshita, Y (1998) Inibitory effect of lichen metabolites and their synthetic analogues on melanin biosynthesis in cultured B-16 mouse melanoma cells. Natural Product Sciences 4: 161–169.Google Scholar
Miao, V, Coeffet-LeGal, M-F, Brown, D, Sinneman, S, Donaldson, G and Davies, J (2001) Genetic approaches to harvesting lichen products. Trends in Biotechnology 19: 349–355.CrossRefGoogle ScholarPubMed
Miyagawa, H, Hamada, N and Ueno, T (1993) Hypostrepsilic acid, a new dibenzofuran from the cultured lichen mycobiont of Evernia esorediosa. Phytochemistry 34: 589–591.Google Scholar
Miyagawa, H, Hamada, N, Sato, M and Ueno, T (1994) Pigments from the cultured lichen mycobionts of Graphis scripta and G. desquamescens. Phytochemistry 36: 1319–1322.CrossRefGoogle Scholar
Molina, MC and Vicente, C (2000) Purification and characterization of two isolectins with arginase activity from the lichen Xanthoria parietina. Journal of Biochemistry and Molecular Biology 33: 300–307.Google Scholar
Mosbach, K (1967) On the biosynthesis of lichen substances. Part 4. The formation of pulvinic acid derivatives by isolated lichen fungi. Acta Chemica Scandinavica 21: 2331–2334.Google Scholar
Müller, K (2001) Pharmaceutically relevant metabolites from lichens. Applied Microbiology and Biotechnology 56: 9–16.Google ScholarPubMed
Nascimento, SC, Pereira, EC, Da Oliveira, AFM, Silva, NH, Boitard, M and Beriel, H (1994) Screening de atividade citotoxica de extratos liquenicos: Cladoniaceae. Acta Botanicae Brasiliensis 8: 97–107.Google Scholar
Neamati, N, Hong, H, Mazumder, A, Wang, S, Sunder, S, Nicklaus, MC, Milne, GW, Proksa, B and Pommier, Y (1997) Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching. Journal of Medical Chemistry 40: 942–951.CrossRefGoogle ScholarPubMed
Neff, GW, Reddy, KR, Durazo, FA, Meyer, D, Marrero, R and Kaplowitz, N (2004) Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid. Journal of Hepatology 41: 1062–1064.Google Scholar
Nicholson, TD, Rudd, BAM, Dawson, M, Lazarus, CM, Simpson, TJ and Cox, RJ (2001) Design and utility of oligonucleotide gene probes for fungal polyketide synthases. Chemistry and Biology 8: 157–178.CrossRefGoogle ScholarPubMed
Nicolaou, KC and Gray, DLF (2004) Total synthesis of hybocarpone and analogues thereof. A facile dimerization of naphtazarins to pentacyclic systems. Journal of the American Chemical Society 126: 607–612.CrossRefGoogle ScholarPubMed
Nishikawa, Y and Ohno, H (1981) Studies on the water-soluble constituents of lichens. IV. Effect of the antitumor lichen-glucans and related derivatives on the phagocytic activity of the reticuloendothelial system in mice. Chemical and Pharmaceutical Bulletin 29: 3407–3410.Google Scholar
Nishikawa, Y, Takeda, T, Shibata, S and Fukuoka, F (1969) Polysaccharides in lichens and fungi. III. Further investigation on the structures and the antitumor activity of the polysaccharides from Gyrophora esculenta Miyoshi and Lasallia papulosa Llano. Chemical and Pharmaceutical Bulletin 17: 1910–1916.CrossRefGoogle Scholar
Nishikawa, Y, Yoshimoto, K, Horiuchi, R, Michishita, K, Okabe, M and Fukuoka, F (1979) Studies on the water-soluble constituents of lichens. III. Changes in antitumor effect caused by modifications of pustulan- and lichenan-type glucans. Chemical and Pharmaceutical Bulletin 27: 2065–2072.Google Scholar
Nybakken, L, Aubert, S and Bilger, W (2004) Epidermal UV-screening of arctic and alpine plants along a latitudinal gradient in Europe. Polar Biology 27: 391–398.CrossRefGoogle Scholar
Ögmundsdóttir, H, Zoëga, GM, Gissurarson, SR, Ingólfsdóttir, K (1998) Anti-proliferative effects of lichen-derived inhibitors of 5-lipoxygenase on malignant cell lines and mitogen-stimulated lymphocytes. Journal of Pharmacy and Pharmacology 50: 107–115.CrossRefGoogle ScholarPubMed
Oksanen, I, Jokela, J, Fewer, DP, Wahlsten, M, Rikkinen, J and Sivonen, K (2004) Discovery of rare and highly toxic microcystins from lichen-associated cyanobacterium Nostoc sp. strain IO-102-I. Applied and Environmental Microbiology 70: 5756–5763.Google Scholar
Okuyama, E, Hossain, CF and Yamazaki, M (1991) Monoamino oxidase inhibitor from a lichen, Solorina crocea (L.) Ach. Shouyakugakuzasshi 45: 159–162.Google Scholar
Okuyama, E, Umeyama, K, Yamazaki, M, Kinoshita, Y and Yamamoto, Y (1995) Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta. Planta Medica 61: 113–115.Google Scholar
Ólafsdóttir, ES, Ingólfsdóttir, K (2001) Polysaccharides from lichens: structural characteristics and biological activity. A review. Planta Medica 67: 199–208.Google Scholar
Ouzzine, H, Le Bazin, MA, Devehat-Lohezic, F, Tomasi, S, Corbel, JC, Boustie, J and Uriac, Ph (2001) Synthèse de conjugués(+) acide usnique-polyamines. Xèmes Conf. européennes du Groupement des Pharmacochimistes de l'ARC Atlantique GP2A, Nantes, 29–30. October.Google Scholar
Pengsuparp, T, Cai, L, Constant, H, Fong, HHS, Lin, LZ, Kinghorn, AD, Pezzuto, JM, Cordell, GA, Ingólfsdóttir, K, Wagner, H and Hughes, SH (1995) Mechanistic evaluation of new plant-derived compounds that inhibits HIV-1 reverse transcriptase. Journal of Natural Products 58: 1024–1031.Google Scholar
Planelles, V and Legaz, ME (1987) Purification and some properties of the secreted arginase of the lichen Evernia prunastri and its regulation by usnic acid. Plant Science 51: 9–16.Google Scholar
Poelt, J and Leuckert, C (1993) Substitution and supplementary addition of secondary products in the evolution of lichenized Ascomycotina. Bibliotheca Lichenologica 53: 201–215.Google Scholar
Rancan, F, Rosan, S, Boehm, K, Fernández, E, Hidalgo, ME, Quilhot, W, Rubio, C, Boehm, F, Piazena, H and Oltmanns, U (2002) Protection against UVB irradiation by natural filters extracted from lichens. Journal of Photochemistry and Photobiology B, Biology 68: 133–139.Google Scholar
Rezanka, T and Dembitsky, V (1999) Novel brominated lipidic compounds from lichens of central Asia. Phytochemistry 51: 963–968.CrossRefGoogle ScholarPubMed
Rezanka, T and Gushina, IA (1999) Brominated depsidones from Acarospora gobiensis, a lichen of Central Asia. Journal of Natural Products 62: 1675–1677.Google Scholar
Rezanka, T and Gushina, IA (2000) Glycosidic compounds of murolic, protocontipatic and allo-murolic acids from lichens of Central Asia. Phytochemistry 54: 635–645.CrossRefGoogle ScholarPubMed
Rezanka, T and Gushina, IA (2001 a) Glycosides esters from lichens of Central Asia. Phytochemistry 58: 509–516.Google Scholar
Rezanka, T and Gushina, IA (2001 b) Further glucosides of lichens' acids from Central Asian lichens. Phytochemistry 56: 181–188.Google Scholar
Rezanka, T and Gushina, IA (2001 c) Macrolactones glycosides of three lichen acids from Acarospora gobiensis, a lichen of Central Asia. Phytochemistry 58: 1281–1287.Google Scholar
Rezanka, T, Jachymova, J and Dembitsky, VM (2003) Prenylated xanthone glucosides from Ural's lichen Umbilicaria proboscidea. Phytochemistry 62: 607–612.Google Scholar
Rezanka, T, Temina, M, Hanus, L and Dembitsky, VM (2004) The tornabeatins, four tetrahydro-2-furanone derivatives from the lichenized ascomycete Tornabea scutellifera (With.) J.R. Laundon. Phytochemistry 65: 2605–2612.CrossRefGoogle ScholarPubMed
Richardson, DHS (1988) Medicinal and other aspects of lichens. In: Galun, M (ed.) CRC Handbook of Lichenology, Vol. 3. Boca Raton, FL: CRC Press 93–108.Google Scholar
Rikkinen, J (1995) What's behind the pretty colours? A study on the photobiology of lichens. Bryobrothera 4: 1–239.Google Scholar
Saklani, A and Upreti, DK (1992) Folk uses of some lichens in Sikkim. Journal of Ethnopharmacology 27: 229–233.Google Scholar
Sankawa, U, Shibuya, M, Ebizuka, Y, Noguchi, H, Kinoshita, T, Iitaka, Y, Endo, A and Kitahara, N (1982) Depside as potent inhibitor of prostaglandin biosynthesis: a new active site model for fatty acid cyclooxygenase. Prostaglandins 24: 21–34.CrossRefGoogle ScholarPubMed
Sauer, M, Lu, P, Sangari, R, Kennedy, S, Polishook, J, Bills, G and An, Z (2002) Estimating polyketide metabolic potential among non-sporulating fungal endophytes of Vaccinium macrocarpum. Mycological Research 106: 460–470.Google Scholar
Schindler, H (1988) Zur Geschichte der Anwendung von Flechten (Lichenes) in der Medizin. Carolinea 46: 31Google Scholar
Schmitt, I, Martin, M, Kautz, S and Lumbsch, Th (2005) Diversity and evolution of secondary metabolite encoding genes in the Pertusariaceae Phytochemistry (in press).Google Scholar
Shahi, SK, Shukla, AC, Uperti, DK and Dikshit, A (2000) Use of lichens as antifungal drugs against superficial fungal infections. Journal of Medicinal and Aromatic Plant Sciences 22(4A)/23(1A) 169–172.Google Scholar
Shahi, SK, Shukla, AC, Dikshit, A and Upreti, DK (2001) Broad spectrum antifungal properties of the lichen Heterodermia leuocomela. Lichenologist 33: 177–179.Google Scholar
Shahi, SK, Patra, M, Dikshit, A and Upreti, DK (2003) Parmelia cirrhatum: a potential source of broad spectrum natural antifungal. Phytotherapy Research 17: 399–400.Google Scholar
Shibamoto, T and Wei, CI (1984) Mutagenicity of lichen constituents. Environmental Mutagenesis 6: 757–762.Google Scholar
Shibata, S (1958) Especial compounds of lichens. Handbuch der Pflanzenphysiologie 10: 560–623.Google Scholar
Shibata, S (2000) Great discoveries in bryology and lichenology—Yasuhiko Asahina (1880–1975.) and his studies on lichenology and chemistry of lichen metabolites. Bryologist 103: 710–719.CrossRefGoogle Scholar
Singh, KK, Upreti, DK and Kaushal, K (2000) Ethnobotanical note on some less known Himalaya lichens. Bulletin of the British Lichen Society 86: 36–37.Google Scholar
Sinnemann, SJ, Andrésson, OS, Brown, DW and Miao, VPW (2000) Cloning and heterologous expression of Solorina crocea pyrG. Current Genetics 37: 333–338.Google Scholar
Solhaug, KA and Gauslaa, Y (2004) Photosynthates stimulate the UV-B induced fungal anthraquinone synthesis in the foliose lichen Xanthoria parietina. Plant, Cell & Environment 27: 167–176.Google Scholar
Solhaug, KA, Gauslaa, Y, Nybakken, L and Bilger, W (2003) UV-induction of sun-screening pigments in lichens. New Phytologist 158: 91–100.Google Scholar
Solheim, B, Johanson, U, Callaghan, TV, Lee, JA, Gwynn-Jones, D, Björn, LO (2002) The nitrogen fixation potential of arctic cryptogram (sic) species is influenced by enhanced UV-B radiation. Oecologia 133: 90–93.Google Scholar
Stepanenko, LS, Krivoshchekova, OE and Skirina, IF (2002) Functions of phenolic secondary metabolites in lichens from far east Russia. Symbiosis 32: 119–131.Google Scholar
Stocker-Wörgötter, E (1998) Culture methods and culture of selected mycobionts and photobionts as exemplified by South American lichens. In: Marcelli, MP, Seaward, MRD (eds) Lichenology in Latin Ameria: History, Current Knowledge and Applications. São Paulo: CETESB, pp. 143–155.Google Scholar
Stocker-Wörgötter, E (2001) Experimental lichenology and microbiology of lichens: culture experiments, secondary chemistry of cultured mycobionts, resynthesis and thallus morphogenesis. The Bryologist 104: 576–581.Google Scholar
Stocker Wörgötter, E (2002 a) Laboratory cultures of selected lichen fungi from Brazil and Chile. Mitteilungen des Instituts für Allgemeine Botanik, Hamburg 30: 253–270.Google Scholar
Stocker-Wörgötter, E (2002 b) Analysis of secondary compounds in cultured mycobionts. In: Kranner, I, Beckett, RP, Varma, AK (eds) Protocols in Lichenology, Culturing, Biochemistry, Ecophysiology and Use in Biomonitoring Springer Lab Manual Berlin: Springer, pp. 296–306.Google Scholar
Stocker-Wörgötter, E and Elix, JA (2004) Experimental studies of lichenized fungi: formation of rare depsides and dibenzofuranes by the culture mycobiont of Bunodophoron patagonicum (Sphaerophoraceae, lichenized Ascomycota). Bibliotheca Lichenologica 88: 659–669.Google Scholar
Stocker-Wörgötter, E, Elix, JA and Grube, M (2004) Secondary chemistry of lichen-forming fungi: chemosyndromic variation and DNA-analyses of cultures and chemotypes in the Ramalina farinacea complex. The Bryologist 107: 152–162.CrossRefGoogle Scholar
Stoll, A, Brack, A and Renz, J (1950) Die Wirkung von Flechtenstoffen auf Tuberkelbakterien und auf einige andere Mikroorganismen. Schweizer Zeitschrift für Allgemeine Pathologie und Bakteriologie 13: 729–751.Google Scholar
Takai, M, Uehara, Y and Beisler, JA (1979) Usnic acid derivatives as potential antineoplastic agents. Journal of Medicinal Chemistry 22: 1380–1384.CrossRefGoogle ScholarPubMed
Tanahashi, K, Kuroishi, M, Kuwahara, A, Nagakura, N and Hamada, N (1997) Four phenolics from the cultured lichen mycobiont of Graphis scripta var pulverulenta. Chemical and Pharmaceutical Bulletin 45: 1183–1185.CrossRefGoogle Scholar
Torres, A, Hochberg, M, Pergament, I, Smoum, R, Niddam, V, Dembitsky, VM, Dor Temina, M, O'Lev, I, Srebnik, O and Enk, CD (2004) A new UV-B absorbing mycosporine with photoprotective activity from the lichenized ascomycete Collema cristatum. European Journal of Biochemistry 271: 780–784.CrossRefGoogle Scholar
Varga, J, Rigo, K, Kocsube, S, Farkas, B and Pal, K (2003) Diversity of polyketide synthase gene sequences in Aspergillus species. Research in Microbiology 154: 593–600.Google Scholar
Vartia, KO (1973) Antibiotics in lichens. In: Ahmadjian, V and Hale, ME (eds) The Lichens. New York: Academic Press, pp. 547–561.Google Scholar
Watanabe, A and Ebizuka, Y (2002) A novel hexaketide naphthalene synthesized by a chimeric polyketide synthase composed of fungal pentaketide and heptaketide synthases. Tetrahedron Letters 43: 843–846.Google Scholar
Wood, S, Huffman, J, Weber, N, Andersen, D, North, J, Murray, B, Sidwell, R and Hughes, B (1990) Antiviral activity of naturally occurring anthraquinones and anthraquinone derivatives. Planta Medica 56: 651–652.Google Scholar
Yamamoto, Y (2000) Screening of biological activities and isolation of biological-active compounds from lichens. Shokubutsu no Kagaku Chosetu 35: 169–179.Google Scholar
Yamamoto, Y, Mizuguchi, R and Yamada, Y (1985) Tissue culture of Usnea rubescens and Ramalina yasudae and production of usnic acid in their cultures. Agricultural and Biological Chemistry 49: 3347–3348.Google Scholar
Yamamoto, Y, Miura, Y, Kinoshita, Y, Higuchi, M, Yamada, Y, Murakami, A, Ohigashi, H and Koshimizu, K (1995) Screening of tissue cultures and thalli of lichens and some of their active constituents for inhibition of tumor promoter-induced Epstein-Barr virus activation. Chemical and Pharmaceutical Bulletin 43: 1388–1390.Google Scholar
Yamamoto, Y, Matsubara, H, Kinoshita, Y, Kinoshita, K, Koyama, K, Takahashi, K, Ahmadjian, V, Kurokawa, T and Yoshimura, I (1996) Naphthazarin derivatives from cultures of the lichen Cladonia cristatella. Phytochemistry 43: 1239–1242.CrossRefGoogle Scholar
Yang, X, Shimizu, Y, Steiner, JR and Clardy, J (1993) Nostoclide I and II, extracellular metabolites from a symbiotic cyanobacterium, Nostoc sp., from the lichen Peltigera canina. Tetrahedron Letters 34: 761–764.Google Scholar
Yoshimura, I, Kinoshita, Y, Yamamoto, Y, Huneck, S and Yamada, Y (1994) Analysis of secondary metabolites from lichen by high performance liquid chromatography with a photodiode array detector. Phytochemical Analysis 5: 197–205.CrossRefGoogle Scholar
Zopf, W (1895) Zur Kenntnis der Flechtenstoffe. Annalen der Chemie 284: 107–132.CrossRefGoogle Scholar