Omics data reveal the unusual asexual-fruiting nature and secondary metabolic potentials of the medicinal fungus Cordyceps cicadae

Abstract

BackgroundAscomycete Cordyceps species have been using as valued traditional Chinese medicines. Particularly, the fruiting bodies of Cordyceps cicadae (syn. Isaria cicadae) have long been utilized for the treatment of chronic kidney disease. However, the genetics and bioactive chemicals in this fungus have been largely unexplored.ResultsIn this study, we performed comprehensive omics analyses of C. cicadae, and found that, in contrast to other Cordyceps fungi, C. cicadae produces asexual fruiting bodies with the production of conidial spores instead of the meiotic ascospores. Genome sequencing and comparative genomic analysis indicate that the protein families encoded by C. cicadae are typical of entomopathogenic fungi, including the expansion of proteases and chitinases for targeting insect hosts. Interestingly, we found that the MAT1-2 mating-type locus of the sequenced strain contains an abnormally truncated MAT1-1-1 gene. Gene deletions revealed that asexual fruiting of C. cicadae is independent of the MAT locus control. RNA-seq transcriptome data also indicate that, compared to growth in a liquid culture, the putative genes involved in mating and meiosis processes were not up-regulated during fungal fruiting, further supporting asexual reproduction in this fungus. The genome of C. cicadae encodes an array of conservative and divergent gene clusters for secondary metabolisms. Based on our analysis, the production of known carcinogenic metabolites by this fungus could be potentially precluded. However, the confirmed production of oosporein raises health concerns about the frequent consumption of fungal fruiting bodies.ConclusionsThe results of this study expand our knowledge of fungal genetics that asexual fruiting can occur independent of the MAT locus control. The obtained genomic and metabolomic data will benefit future investigations of this fungus for medicinal uses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4060-4) contains supplementary material, which is available to authorized users.

Cyclosporine Biosynthesis in Tolypocladium inflatum Benefits Fungal Adaptation to the Environment

“…For induction of CsA production, the WT or mutants was induced in the cyclosporine (CSN) induction medium containing fructose (fructose CSN induction medium) [fructose, 30 g/liter; (NH 4 ) 2 HPO 4 , 6 g/liter; yeast extract, 5 g/liter; CaCl 2 ·2H 2 O, 1.32 g/liter; MgSO 4 ·7H 2 O, 2.05 g/liter; FeSO 4 ·7H 2 O, 27.4 mg/liter; ZnSO 4 ·7H 2 O, 17.8 mg/liter; CoCl 2 ·6H 2 O, 27.5 mg/liter; CuSO 4 ·5H 2 O, 3.1 mg/liter] adjusted from a previous study (17). The strains of Aspergillus flavus (NRRL 3357), Metarhizium robertsii (ARSEF 23) (33), Cordyceps cicadae (CCAD02) (34), Cordyceps militaris (Cm01) (35), and Beauveria brongniartii (RCEF 3172) (36) were used for antifungal assays between WT and null mutants of T. inflatum . The standards of cyclosporin A (CsA) and d -Ala were ordered from Sigma-Aldrich (USA), and CsB and CsC were purchased from Santa Cruz Biotechnology (USA).…”

“…Together with SimC, there are 10 cyclophilin genes encoded in the genome of T. inflatum (1). Different cyclophilins were selected from the close relatives of T. inflatum for phylogenetic analysis, including those from the insect pathogens Beauveria bassiana (44), Metahizium robertsii (33), Cordyceps militaris (35), Cordyceps cicadae (34), and Ophiocordyceps sinensis (45). A NJ tree was generated using the same parameters indicated above.…”

The complete mitochondrial genome of the Chan‐hua fungus Isaria cicadae: a tale of intron evolution in Cordycipitaceae

“…For instance, seven tenths (90/130) of the total nucleotide records of I. cicadae in GenBank (which erroneously accepted Cordyceps cicadae as the name for the Chan-hua fungus) as of January 2019 are ITS records of different isolates. Most recently, a comprehensive omics analyses of I. cicadae was carried out using the isolate CCAD02 (Lu et al, 2017). Nevertheless, the mitogenome information of the fungus is still lacking.…”

Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae

“…Isaria cicadae , named by Miquel in 1838, is parasitic on the nymph of cicada and can form cordyceps, which are called Chan Hua in Chinese, meaning the flower of cicadae (Chen, Li, & Chen, ; Massee, ). Chan Hua also has many other names, such as Cordyceps cicadae , Cordyceps sinclairii , Isaria sinclairii and Paecilomyces cicadae (Chen et al, ; Hsu, Jhou, Yeh, Chen, & Chen, ; Kobayasi & Shimizu, ; Lu et al, ). The newest taxonomy system classifies Chan Hua as I. cicadae Miquel because the fruiting body (coremium) of the cordyceps is asexual (Lu et al, ; Sung et al, ).…”

“…Chan Hua also has many other names, such as Cordyceps cicadae , Cordyceps sinclairii , Isaria sinclairii and Paecilomyces cicadae (Chen et al, ; Hsu, Jhou, Yeh, Chen, & Chen, ; Kobayasi & Shimizu, ; Lu et al, ). The newest taxonomy system classifies Chan Hua as I. cicadae Miquel because the fruiting body (coremium) of the cordyceps is asexual (Lu et al, ; Sung et al, ). Its use as a herbal medicine was recorded in many famous ancient Chinese books such as Lei Gong Pao Zhi Lun ( Lei's Treatise on Preparing Drugs ), which was written during the Northern and Southern Dynasties of China (AD 420–589), the Tu Jing Ben Cao ( Map of Materia of China ), published in AD 1061, and the Ben Cao Gang Mu ( Chinese Compendium of Materia Medica ), which appeared in AD 1596 (Chen et al, ; Hsu et al, ).…”