Immunosuppressive Polyketides from Mantis-Associated Daldinia eschscholzii

Abstract

Polyketides with unknown architectures are highly desired for the discovery of new drugs and agrochemicals. Here, the mantis-associated Daldinia eschscholzii, a fungus known to produce immunosuppressants dalesconols A and B, was found to simultaneously generate four novel skeletons capable of shaping the unusual chemistry of the fungal polyketides, of which seven were structurally unique and substantially immunosuppressive. In particular, the scaled-up fermentation of the microbe enabled the structural characterization of minor or "transitional" intermediate polyketides that allowed the reasonable recognition of the four biosynthetic pathways initiated by condensations of four, five, six and eight acetate units, respectively. Furthermore, the decarbonylation reaction of triketone, as in the case of daeschol A, was described for the first time, in addition to the structural correction of sporothrin C and nodulone. The work provided a set of novel immunosuppressive molecules that are of significance to drug discovery.

Naphthol radical couplings determine structural features and enantiomeric excess of dalesconols in Daldinia eschscholzii

“…Scrutinizing the aromatization and substitution patterns of dalesconols A-C (1-3), we hypothesized that they could be biosynthetically constructed via a combination of three naphthol residues with a carbon eliminated through an autooxidation reaction we witnessed recently 6 . This assumption was substantiated by the fact that the fungus produced as well naphthol-dimerized derivatives such as dihydrosphaerolone and 2,16-dihydroxyl-benzo[j]fluoranthene (a new potent immunosuppressor) 5,6 .…”

“…This assumption was substantiated by the fact that the fungus produced as well naphthol-dimerized derivatives such as dihydrosphaerolone and 2,16-dihydroxyl-benzo[j]fluoranthene (a new potent immunosuppressor) 5,6 . To confirm this prediction, we searched for the genetic evidence to lead to the identification of pksTL, a gene encoding 1,3,6,8-tetrahydroxynaphthalene synthase (4HNS).…”

Isolation of Bioactive Metabolites Producing Fungal Strains From Milk Products and Milk Industries of Raipur District

“…[6] Daldinia eschscholzii, isolated from the gut of the mantis species Tenodera aridifolia, was reported to simultaneously generate four novel skeletons and seven structurally unique metabolites that have the potential to become immune inhibitors. [7,8] [11]…”

Daldinia eschscholtzii (Ascomycota, Xylariaceae) isolated from the Brazilian Amazon: taxonomic features and mycelial growth conditions

“…Two years later, daeschol A, dalesconol C, 2, 16-dihydroxyl-benzo[j]fluoranthene and dalmanol A were isolated by the first time from mantis-associated D. eschscholtzii (Zhang et al 2011). Recently, helicascolide C, a new lactone with fungistatic activity against Cladosporium cucumerinum was isolated together with helicascolide A from an Indonesian marine algicolous-associated D. eschscholtzii strain (Tarman et al 2012).…”