Genome-scale metabolic network of Cordyceps militaris useful for comparative analysis of entomopathogenic fungi

Vongsangnak, Wanwipa; Raethong, Nachon; Mujchariyakul, Warasinee; Nguyen, Nam Ninh; Leong, Hon Wai; Laoteng, Kobkul

doi:10.1016/j.gene.2017.05.027

Cited by 34 publications

(23 citation statements)

References 42 publications

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“…This indicated that additives like L-alanine may improve cordycepin production by imparting amino acid conversion. Besides, significant changes in the KEGG pathway ko01100 were confirmed as previously mentioned (Vongsangnak et al, 2017). Glycolysis, the pentose phosphate pathway, and the citrate cycle were involved in the biosynthesis of cordycepin by supplying energy for any relevant bioactivities.…”

Section: Discussionsupporting

confidence: 76%

“…The CCM_03940 was the only significantly up-regulated one at the transcriptional level. CCM_01353, identified as a unique adenylate kinase gene in C. militaris in a previous report (Vongsangnak et al, 2017), along with the other three genes, both showed no significant difference between the experimental group and control. Another enzyme verified (Kuo et al, 2015) to be involved in cordycepin synthesis was adenine phosphoribosyltransferase (APRTase) (EC 2.4.2.7), which transforms adenine into AMP.…”

Section: Putative Cordycepin Metabolism Pathwaymentioning

confidence: 74%

“…Since the cordycepin production was significantly improved by L-alanine addition, DEGs related to cordycepin synthesis were carefully identified by comparison to the previously reported purine metabolic pathway constructed by Zheng et al (2011), and Vongsangnak et al (2017), and the cordycepin biosynthesis gene cassette presented by Xia et al (2017). Finally, the whole cordycepin metabolic network in C. militaris was predicted ( Figure 5).…”

Section: Putative Cordycepin Metabolism Pathwaymentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 76%

Section: Putative Cordycepin Metabolism Pathwaymentioning

confidence: 74%

Section: Putative Cordycepin Metabolism Pathwaymentioning

confidence: 99%

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

et al. 2020

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“…Emphasizing the biosynthesis of important metabolites (i.e., carotenoid and cordycepin), the GSMN of C. militaris was systemically improved by introducing the genes and their associated metabolites as well as biochemical reactions involved in the carotenoid biosynthetic pathway into the previous study reported by Raethong et al [ 15 ]. Compared to the earlier network ( i NR1329) [ 15 ], a total of 138 additional genes were identified from the GSMN of C. militaris ( i WV1170) [ 31 ] together with extensive data mining from different databases. These included the genes related to the light-induced carotenoid formation from the previous studies [ 7 , 8 ].…”

Section: Resultsmentioning

confidence: 99%

“…To uncover the reporter metabolites, the previous genome-scale metabolic network (GSMN) of C. militaris ( i NR1329) [ 15 ] was improved by introducing the genes and their associated metabolites and biochemical reactions involved in carotenoid biosynthetic pathway and sugar transport system, as previously reported [ 7 , 14 , 30 ]. The additional genes identified from the first GSMN of C. militaris ( i WV1170) [ 31 ] together with extensive data mining from different databases were newly added into i NR1329, thereby enhancing the gene content of the improved GSMN in this study. Then, the KEGG annotation and the improved GSMN of C. militaris as scaffolds were integrated with the list of DEGs obtained from the glucose cultures grown under the light-programming and dark conditions for identification of the key pathways and metabolites using the consensus gene-set enrichment analysis and reporter metabolites analysis, respectively.…”

Section: Methodsmentioning

confidence: 99%

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

Thananusak

Laoteng

Raethong

et al. 2020

Biology

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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.

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Poly‐pathways metabolomics for high‐yielding cordycepin of Cordyceps militaris

Sun

Wang

et al. 2022

Biomedical Chromatography

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Cordycepin is an important quality control marker in Cordyceps militaris. This study aimed to explain the metabolic mechanisms for high‐yielding cordycepin of C. militaris. In this study, high‐yielding strains of cordycepin were obtained by ultraviolet mutagenesis, and the polysaccharide and protein contents were also changed. In high‐yielding strains, the protein content significantly increased, whereas the polysaccharide content decreased. Simultaneously, metabolic differences for high‐ and low‐yielding cordycepin strains were detected by metabolomics. Metabolomics results showed that the relative content of most metabolites decreased in high‐yielding cordycepin strains. Various metabolic pathways have been altered in high‐yielding cordycepin strains, such as the citric acid cycle, purine metabolism, and pyrimidine metabolism, leading to an increase in cordycepin content. In addition, changes in metabolic poly‐pathways related to polysaccharide and protein synthesis, such as galactose metabolism and amino acid metabolism, promoted an increase in cordycepin content. This study analyzes the high yield of cordycepin in C. militaris at the metabolic level and provides a theoretical basis for further increasing cordycepin content.

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Genome-scale metabolic network of Cordyceps militaris useful for comparative analysis of entomopathogenic fungi

Cited by 34 publications

References 42 publications

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

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

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

Poly‐pathways metabolomics for high‐yielding cordycepin of Cordyceps militaris

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