Fungal natural products-the mushroom perspective.

Abstract

Among the first documented studies on the chemistry of fungal natural products were descriptions of quinoid pigments, i.e., the L-tyrosine- and L-phenylalanine-derived terphenylquinones atromentin and polyporic acid, respectively. The isolation of these compounds from mushroom fruiting bodies (basidiomes) was published around 1877 by Stahlschmidt and Thorner. Ever since, organic chemists embraced basidiomycetes as a prolific source of bioactive compounds and investigated these fungi with regard to compound isolation, structure elucidation, and synthesis (Gill and Steglich, 1987; Zhou and Liu, 2010; De Silva et al., 2013 and previous reviews referenced therein, Lorenzen and Anke, 1998; Richter et al., in press). Mushrooms seem to be particularly talented in producing unique terpenoids, and the molecular background behind the biosynthesis of some of those compounds has only recently been elucidated (Quin et al., 2014). Prominent examples of basidiomycete metabolites for lead structures in agrochemistry and drug research are, among others, the strobilurins, i.e., agriculturally used s-methoxyacrylate fungicides from cultures of Mycena, Oudemansiella, Strobilurus, Xerula and several other basidiomycete genera (Sauter et al., 1999, Figure 1). Other examples are the pleuromutilins, the illudins, and the omphalotins (Figure ​(Figure1).1). The pleuromutilins from cultures of species that are now placed in the genera Clitopilus and Omphalina served as scaffold for the development of the semisynthetic antibacterial antibiotic retapamulin (Kirst, 2013) which is clinically used for topical treatment of infections with Staphylococcus aureus. The illudins from Lampteromyces and Omphalotus species (Omphalotaceae) are sesquiterpenes featuring an unusual cyclopropane ring and are currently developed as anticancer drugs (Tanasova and Sturla, 2012). The omphalotins are cyclopeptides with pronounced nematicidal activites against root knot nematodes (Buchel et al., 1998), which are also exclusively found in the Omphalotaceae. Recently, the blazeispirols from Agaricus subrufescens were discovered as strong and selective agonists of the Liver X receptor (LXR alpha). Concurrently, relevant in vivo effects of blazeispirols in a mouse model were observed which might give rise to the development of a new anti-hypercholesterolemic agent from cultures of a medicinal mushroom (Grothe et al., 2011).