Transcriptome Analysis Reveals the Flexibility of Cordycepin Network in Cordyceps militaris Activated by L-Alanine Addition

Abstract

Cordycepin, isolated from the traditional medicinal fungus Cordyceps militaris, has gained much attention due to its various clinical functions. Previous reports of L-alanine addition could significantly improve cordycepin production, but the molecular mechanism remains unknown. In this study, transcriptome analysis of C. militaris with doubled cordycepin production induced by L-alanine addition provides an insight into the flexibility of the cordycepin network. The biopathways of energy generation and amino acid conversion were activated so that cordycepin substrate generation was consequently improved. Specific genes of rate-limiting enzymes in these pathways, as well as related transcription factors, were figured out. Two key Zn2Cys6-type transcription factors CmTf1 and CmTf2 were verified to play the roles of doubling the cordycepin production by overexpression of their coding genes in C. militaris wild type. These results provide a complete map of the cordycepin network in C. militaris with a distinct understanding of the flexibility of joints, giving a better foundation for increasing cordycepin yield and strain breeding in the future.

Biomass and Cordycepin Production by the Medicinal Mushroom Cordyceps militaris—A Review of Various Aspects and Recent Trends towards the Exploitation of a Valuable Fungus

“…Furthermore, in order to optimize C. militaris productivity, many parameters have already been examined through numerous pertinent studies that will be suitably outlined and discussed in the present review. Most of them focused on developing suitable methodologies and interventions to avoid (or minimize) culture degeneration [21][22][23][24][25][26][27][28][29][30][31], on improving ascomata and mycelia production [12,15,[32][33][34][35][36], and/or on enhancing cordycepin output by adopting various approaches and the use of both solid and liquid substrates [12,15,23,32,[37][38][39][40][41][42][43][44][45][46][47]. In addition, the application of genetic engineering breakthrough technologies has resulted in a considerable improvement in C. militaris biomass content in various metabolites, including cordycepin [37,[48][49][50][51].…”

Transcriptomic Responses of Cordyceps militaris to Salt Treatment During Cordycepins Production

“…Since C. militaris produces a variety of bioactive compounds with functional properties, it has long been utilized as a dietary supplement (tonic food) or herbal medicine for the pharmaceutical and cosmetics industries for many years ( 4 , 5 ). Various bioactive metabolites isolated from C. militaris , such as cordycepin (3′-deoxyadenosine) ( 6 ), cordycepic acid, carotenoid, ergosterol, and cordyceps polysaccharide ( 7 ), have been explored extensively for extending its applications; particularly, several of them are extracted and made into tablets and capsules ( 8 ). In addition, fermentation and downstream processes or other bioprocess developments have permitted a prospect in the production of these specific bioactive metabolites as functional ingredients for diversified applications ( 9 ).…”

The Chemical Ecology Approach to Reveal Fungal Metabolites for Arthropod Pest Management

“…Phytotoxic properties cordycepin were reported to propose it as a natural herbicide [ 81 ]. Although cordycepin can be produced on an industrial scale for medical purposes [ 82 ], its use as an insecticide is unlikely to be appropriate.…”