Lichens—a promising source of bioactive secondary metabolites Joe¨l Boustie 1 * and Martin Grube 2 1 Institut de Chimie de Rennes, Equipe: Substances Liche´niques et Photoprotection, UFR Pharmacie, 2 av du Pr. Le´on Bernard (CS 34317), 35043 Rennes Ce´dex, France and 2 Institute of Plant Sciences, Karl-Franzens-University Graz, Holteigasse 6, 8010 Graz, Austria Received 3 February 2005; Accepted 25 April 2005 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 num- bers 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 determi- nation 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 pat- terns 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 suit- able amounts of unique lichen compounds. Keywords: bioactivity; biosynthesis; drugs; lichens; metabolites, phylogeny; phytochemistry Introduction Lichens are characterized as a stable and self-supporting association between fungi—the mycobionts—and photo- autotrophic, algal partners—the photobionts. Since the mycobiont is unique in the symbiotic association and usually dominates the association, lichens are tradition- ally classified as a life-form of fungi. As an apparently successful form of fungal symbioses, the lichen-forming habit is maintained by one-fifth of all fungi, which includes more than ca 40% of ascomycetes, but only a few basidiomycetes. About 18,500 different lichen species have been described all over the world. They may grow under rather diverse and sometimes extreme ecological conditions. Lichens can be found in very cold and dry *Corresponding author. E-mail: joel.boustie@univ-rennes1.fr q NIAB 2005 ISSN 1479-2621 Plant Genetic Resources 3(2); 273–287 DOI: 10.1079/PGR200572