Insight into cordycepin biosynthesis of Cordyceps militaris: Comparison between a liquid surface culture and a submerged culture through transcriptomic analysis

Suparmin, Ahmad; Kato, Tatsuya; Dohra, Hideo; Park, Enoch Y.

doi:10.1371/journal.pone.0187052

Cited by 34 publications

(32 citation statements)

References 42 publications

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“…To perform transcriptomic analysis, RNA was extracted from aerial and submerged mycelia following 5, 12 and 19 days of culture. The aerial and submerged mycelia of the 5th day were used to control of the transcriptome analysis, because the mycelia began forming aerial mycelia but did not cover the surface of the medium, and cordycepin production had not yet started (Suparmin et al, ). The results revealed a total of 710 and 1682 DEGs using triplicate samples and a threshold set up of four‐fold change (log2 FC ≥2) and false discovery rate (FDR ≤5%) for the aerial and submerged mycelia, respectively, following 12 days of culture.…”

Section: Resultsmentioning

confidence: 99%

“…The aerial and submerged mycelia of the 5th day were used to control of the transcriptome analysis, because the mycelia began forming aerial mycelia but did not cover the surface of the medium, and cordycepin production had not yet started (Suparmin et al, 2017).…”

Section: Overview Of the Differentially Expressed Genes (Degs) In Tmentioning

confidence: 99%

“…We recently reported that cordycepin achieved the highest production in the 15 days of the liquid surface culture of C. militaris and hypothesis that cordycepin biosynthesis coincides with hypoxia (Suparmin et al, 2017). The primary objective of this study was to clarify the understanding of cordycepin production in the liquid surface culture, examine the hypoxic condition in detail and determine whether the aerial or submerged mycelia contributed to cordycepin biosynthesis.…”

Section: Global Metabolism Changes In Submerged Myceliamentioning

confidence: 99%

“…Previously, we reported an RNA sequencing (RNA‐Seq) analysis of differentially expressed genes (DEGs) between liquid surface and submerged cultures of C. militaris. Surprisingly, the analysis revealed that cordycepin was produced significantly higher in the liquid surface culture than in the submerged culture (Suparmin, Kato, Dohra, & Park, ). SAICAR synthase (CCM_04437) and some oxidoreductase activities were significantly upregulated in the liquid surface culture.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic comparison of aerial and submerged mycelia formed in the liquid surface culture of Cordyceps militaris

et al. 2019

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An entomopathogenic fungus, Cordyceps sp. has been known to produce cordycepin which is a purine nucleoside antimetabolite and antibiotic with potential anticancer, antioxidant and anti‐inflammatory activities. Interestingly, Cordyceps militaris produces significantly higher amount in a liquid surface culture than in a submerged culture. The liquid surface culture consists of mycelia growing into the air (aerial mycelia) and mycelia growing toward the bottom into the medium (submerged mycelia). In this study, to clarify roles of aerial and submerged mycelia of C. militaris in the cordycepin production the difference in metabolism between these mycelia was investigated. From transcriptomic analyses of the aerial and submerged mycelia at the culture of 5, 12 and 19 days, the metabolism of the submerged mycelia switched from the oxidative phosphorylation to the fermentation pathway. This activated the pentose phosphate pathway to provide building block materials for the nucleotide biosynthetic pathway. Under hypoxic conditions, the 5‐aminolevulinic acid synthase (CCM_01504), delta‐aminolevulinic acid dehydratase (CCM_00935), coproporphyrinogen III oxidase (CCM_07483) and cytochrome c oxidase 15 (CCM_05057) genes of heme biosynthesis were significantly upregulated. In addition, the liquid surface culture revealed that metabolite coproporhyrinogen III and glycine, the product and precursor of heme, were increased at 12th day and decreased at 19th day, respectively. These results indicate that the submerged mycelia induce the activation of iron acquisition, the ergosterol biosynthetic pathway, and the iron cluster genes of cordycepin biosynthesis in a hypoxic condition. Even though, the expression of the cluster genes of cordycepin biosynthesis was not significantly different in both types of mycelia.

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Section: Resultsmentioning

confidence: 99%

Section: Overview Of the Differentially Expressed Genes (Degs) In Tmentioning

confidence: 99%

Section: Global Metabolism Changes In Submerged Myceliamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic comparison of aerial and submerged mycelia formed in the liquid surface culture of Cordyceps militaris

et al. 2019

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“…When this fungus inoculated in liquid static culture the submerged mycelia were grown towards the bottom into the medium, and the hypha on the surface of the culture grow into the air and form aerial mycelia after a period of incubation (Figure 1). As we previously reported that cordycepin was produced higher in liquid static than submerged culture [5]. These submerged mycelia that have a direct contact with the medium which might contribute to the secretion of cordycepin.…”

Section: National University Corporationmentioning

confidence: 67%

Intercorrelation mechanism of Hypoxia and Cordycepin Biosynthesis in Zombie fungus

Suparmin

Kato

Takemoto

et al. 2020

Access Microbiology

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Cordycepin is an anticancer metabolite produces by a zombie fungus species of Cordyceps militaris. They are capable to infect and hijack insect’s nervous neuron system. Hypoxic environment commonly must be faced by the pathogenic fungus during infection either this zombie fungus. They activate oxygen sensing mode, heme, siderophore, and sterol biosynthesis to overcome it. Underlined our previous study that liquid surfaced culture of C. militaris NBRC103752 produced a higher amount of cordycepin than submerged culture, suggesting that hypoxic conditions might induce it. However, when and how the mechanism of cordycepin production started in liquid surfaced culture is not understood, yet. In our present study, the combination of transcriptomics and gas chromatography-mass spectrometry were carried out during the production phases of cordycepin (5d, 12d, and 19d of incubation periods) and the mechanism of cordycepin production was figured out. The expression of genes in the fermentation pathway and the oxidative phosphorylation pathway were significantly upregulated and down regulated, respectively. Expression of four genes in the heme biosynthesis, including 5-aminolevulinic acid synthase (CCM_01504), delta-aminolevulinic acid dehydratase (CCM_00935), coproporphyrinogen III oxidase (CCM_07483) and cytochrome c oxidase15 (CCM_05057) were upregulated at the beginning of the exponential phase (12d). Further, the activation of Zn(2)-C6 transcription factor that regulates the iron acquisition and ergosterol biosynthesis significantly upregulated and a metabolite reporter adenosine was detected only at 12d. The results in the present study show the correlation between hypoxia and the accumulation of heme before cordycepin biosynthesis.

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Production and stability of pigments by Talaromyces purpurogenus LC128689 in an alternating air phase–liquid phase cultivation system

Ugwu

Ogbonna

et al. 2021

Biotech and App Biochem

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Effects of carbon source, nitrogen source, and alternatingly submerging the cells and exposing to gaseous oxygen on pigment production by Talaromyces purpurogenus LC128689, as well as pH, temperature, and UV stability of the pigments were investigated. Although fructose supported higher cell growth, a mixture of glucose and glycerol resulted in higher pigment production. Out of the organic and inorganic nitrogen sources investigated, peptone gave the highest cell concentration (7.2 ± 1.1 g/L) and pigment production (p ≤ 0 .05). The cells were then immobilized in loofa sponge and cultivated under alternating liquid phaseair phase (ALAP) system whereby the cells were alternatingly submerged and exposed to gaseous oxygen. After 20 days of cultivation, the concentrations of the red, orange, and yellow pigments were 30.15 AU 500 nm , 15 AU 460 nm , and 6.25 AU 400 nm , respectively. In comparison with submerged culture in flasks, the red and orange pigments were 100% and 50% higher (p ≤ 0.05) in ALAP system. On the other hand, the yellow pigment was 100% higher in flask cultures than in ALAP. The three pigments were stable within a pH range of 2-12, retained more than 80% of their color intensity after autoclaving at (121 • C and 1.0 atm) for 15 min and exposure to UV (3 uW/cm 2 ) for 24 h.

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Insight into cordycepin biosynthesis of Cordyceps militaris: Comparison between a liquid surface culture and a submerged culture through transcriptomic analysis

Cited by 34 publications

References 42 publications

Metabolic comparison of aerial and submerged mycelia formed in the liquid surface culture of Cordyceps militaris

Metabolic comparison of aerial and submerged mycelia formed in the liquid surface culture of Cordyceps militaris

Intercorrelation mechanism of Hypoxia and Cordycepin Biosynthesis in Zombie fungus

Production and stability of pigments by Talaromyces purpurogenus LC128689 in an alternating air phase–liquid phase cultivation system

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