Metabolic Responses of Carotenoid and Cordycepin Biosynthetic Pathways in Cordyceps militaris under Light-Programming Exposure through Genome-Wide Transcriptional Analysis

Abstract

Cordyceps militaris is currently exploited for commercial production of specialty products as its biomass constituents are enriched in bioactive compounds, such as cordycepin. The rational process development is important for economically feasible production of high quality bioproducts. Light is an abiotic factor affecting the cultivation process of this entomopathogenic fungus, particularly in its carotenoid formation. To uncover the cell response to light exposure, this study aimed to systematically investigate the metabolic responses of C. militaris strain TBRC6039 using integrative genome-wide transcriptome and genome-scale metabolic network (GSMN)-driven analysis. The genome-wide transcriptome analysis showed 8747 expressed genes in the glucose and sucrose cultures grown under light-programming and dark conditions. Of them, 689 differentially expressed genes were significant in response to the light-programming exposure. Through integration with the GSMN-driven analysis using the improved network (iRT1467), the reporter metabolites, e.g., adenosine-5′-monophosphate (AMP) and 2-oxoglutarate, were identified when cultivated under the carotenoid-producing condition controlled by light-programming exposure, linking to up-regulations of the metabolic genes involved in glyoxalase system, as well as cordycepin and carotenoid biosynthesis. These results indicated that C. militaris had a metabolic control in acclimatization to light exposure through transcriptional co-regulation, which supported the cell growth and cordycepin production in addition to the accumulation of carotenoid as a photo-protective bio-pigment. This study provides a perspective in manipulating the metabolic fluxes towards the target metabolites through either genetic or physiological approaches.

Transcriptomic Responses of Cordyceps militaris to Salt Treatment During Cordycepins Production

“…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 ).…”

Construction of Light-Responsive Gene Regulatory Network for Growth, Development and Secondary Metabolite Production in Cordyceps militaris

“…RNA sequencing reads of C. militaris strain TBRC6039 in light condition (BioProject: PRJNA579732, BioSample SAMN13118310) and dark condition (BioProject: PRJNA416937, BioSample SAMN07969453) were retrieved from previous studies [ 20 , 33 ]. Reads were filtered by the quality control at the Phred-score ≥30, yielding qualified reads of 88.68% and 94.46% in light and dark condition samples, respectively.…”

“…Parameters of the simulation were set as follows: the percentage of the total number of reads ( pnr ) = 0.2, the number of simulated samples ( nss ) = 10 and variability in sample total reads of simulated samples ( v ) = 0.02. These parameters were set similarly to a previous analysis [ 20 ], except the value of nss , which was strictly set to reduce the false positives. NOISeq-sim calculates the probability of differential expression ( q ), which was set to be q ≥ 0.9 for DEGs in this study.…”

“…to increase the production of beneficial metabolites has gained much attention [ 14 , 15 ] based on advanced systematic analysis [ 16 , 17 , 18 ]. Previous studies have shown that light strongly affects the fruiting body formation and cordycepin and carotenoid synthesis in C. militaris [ 6 , 13 , 19 ], especially the carotenoid metabolism, which is increased under light-programming exposure [ 20 ].…”

Broad Efficacy of Scavenging Free Radicals: Cordyceps sp.

“…The genome-wide transcriptome assessment showed 8747 imparted characteristics in the glucose and sucrose social orders created under light-programming and faint conditions. Cordycepin curbed cell improvement and set off apoptosis in U87MG cells with wild-type p53, yet not in T98G cells with freak type p53 [54,55] (Figure 1).…”