The metabolome of lichens and their partners, a source of bioactive compounds?

Lichens are mostly commonly thought to represent a mutualistic association between a mycobiont (fungus) and a photobiont (chlorophyte or/and cyanobacterium). This association is responsible for the production of original secondary metabolites via various biosynthetic pathways [1]. Some of them have interesting biological activities: cytotoxic, antibacterial, antifungal, photoprotective properties [1 – 2-3]. Lichens also include diverse lichen-inhabiting (lichenicolous and endophytic) fungi as well as a plethora of bacteria, apart from the cyanobacterium [4]. Lichens have apparently evolved effective means to control their inhabitants, by producing metabolites acting as a communication and controlling system. Antibiotic effect of a number of lichen metabolites against gram-positive bacteria has been already reported [3]. Recent studies by molecular approaches demonstrated that the bacterial communities associated with lichens are dominated by Alphaproteobacteria [5] but also highlighted the presence of Actinobacteria [6]. Lichen-associated bacteria could themselves be an untapped source of highly effective new secondary metabolites. Evidence for this was found already: a Streptomyces isolate from reindeer lichens (Cladonia uncialis) produced uncialamycin, a new enediyne [7] with strong antibacterial activity against both Gram-positive and Gram-negative human pathogens and new alkaloids cladoniamides A-G. Cladoniamide G exhibited significant in vitro cytotoxicity against human breast cancer MCF-7 cells [8]. Two other Streptomyces species have been isolated from lichen species and produced novel cytotoxic compounds: chlorinated anthraquinonic angucycline [9] and aminocoumarines structurally closed to novabiocine [10]. Lichen-forming fungi have been reported as a promising source of a variety of secondary metabolites showing significant biological activities [11]. Recent studies revealed thus the interest of cultured mycobiont for the production cytotoxic decalin-type polyketides [12] or cytotoxic perylenequinones [13]. We will present an overview of the results of our laboratory in the discovery of interesting bioactive compounds (cytotoxic, antibacterial... such as dibenzofuranes, diketopiperazines, phenoxazine and pyrrole derivatives...) from these underexplored mini-ecosystem organisms (whole lichens, isolated bacteria) using various approaches from classical methods to metabolomic tools.

Acknowledgements: Thanks to the financial support CNRS, INSA, ANR, to the PNSCM team and to my collaborators D. Parrot, Dr N. Legrave, Dr D. Delmail.

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