Abstract
Ophiocordyceps sinensis has been used as a traditional medicine or healthy food in China for thousands of years. Hirsutella sinensis was reported as the only correct anamorph of O. sinensis. It is reported that the laboratory-grown H. sinensis mycelium has similar clinical efficacy and less associated toxicity compared to the wild O. sinensis. The research of the H. sinensis is becoming more and more important and urgent. To gain deeper insight into the biological and pharmacological mechanisms, we sequenced the genome of H. sinensis. The genome of H. sinensis (102.72 Mb) was obtained for the first time, with > 99% coverage. 10,200 protein-encoding genes were predicted based on the genome sequence. A detailed secondary metabolism analysis and structure verification of the main ingredients were performed, and the biosynthesis pathways of seven ingredients (mannitol, cordycepin, purine nucleotides, pyrimidine nucleotides, unsaturated fatty acid, cordyceps polysaccharide and sphingolipid) were predicted and drawn. Furthermore, infection process and mechanism of H. sinensis were studied and elaborated in this article. The enzymes involved in the infection mechanism were also predicted, cloned and expressed to verify the mechanism. The genes and proteins were predicted and annotated based on the genome sequence. The pathways of several active components in H. sinensis were predicted and key enzymes were confirmed. The work presented here would improve the understanding of the genetic basis of this organism, and contribute to further research, production and application of H. sinensis.
Highlights
Ophiocordyceps sinensis, a fungus that parasitizes Lepidoptera larvae, has been used as a traditional medicine or healthy food in China for thousands of years (Zhang et al 2012; Zhu et al 1998)
Identification of ORFan genes We identified the ORFans in the H. sinensis genome by a BLAST filtering approach (BLASTP, e-value < 0.01), and compared all predicted peptide sequences to all available peptide sequences in fully annotated H. sinensis genome
We identified ORFans originated by duplication events using all-against-all BLASTP and BLASTN searches for all ORFans versus non-ORFans within the H. sinensis genome, and identified orthologs containing frame shifts using BLASTN against all sequenced H. sinensis genome coding sequences
Summary
Ophiocordyceps sinensis, a fungus that parasitizes Lepidoptera larvae, has been used as a traditional medicine or healthy food in China for thousands of years (Zhang et al 2012; Zhu et al 1998). The use of O. sinensis has a long history in traditional Chinese medicine and Tibetan medicine (Sharma 2004; Winkler 2008). It is found that H. sinensis has activities to modulate immune responses, inhibit tumor cell proliferation, enhance hepatic function, regulate insulin sensitivity, decrease plasma cholesterol levels and modulate steroidogenesis (Cheung et al 2009; Fu et al 2018; He et al 2013; Lu et al 2019). O. sinensis can only be obtained by field collection, so wild O. sinensis was called as
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