Abstract
Ganoderma lucidum, which contains numerous biologically active compounds, is known worldwide as a medicinal basidiomycete. Because of its application for the prevention and treatment of various diseases, most of artificially cultivated G. lucidum is output to many countries as food, tea, and dietary supplements for further processing. Methyl jasmonate (MeJA) has been reported as a compound that can induce ganoderic acid (GA) biosynthesis, an important secondary metabolite of G. lucidum. Herein, MeJA was found to increase the intracellular level of nitric oxide (NO). In addition, upregulation of GA biosynthesis in the presence of MeJA was abolished when NO was depleted from the culture. This result demonstrated that MeJA-regulated GA biosynthesis might occur via NO signaling. To elucidate the underlying mechanism, we used gene-silenced strains of nitrate reductase (NR) and the inhibitor of NR to illustrate the role of NO in MeJA induction. The results indicated that the increase in GA biosynthesis induced by MeJA was activated by NR-generated NO. Furthermore, the findings indicated that the reduction of NO could induce GA levels in the control group, but NO could also activate GA biosynthesis upon MeJA treatment. Further results indicated that NR silencing reversed the increased enzymatic activity of NOX to generate ROS due to MeJA induction. Importantly, our results highlight the NR-generated NO functions in signaling crosstalk between reactive oxygen species and MeJA. These results provide a good opportunity to determine the potential pathway linking NO to the ROS signaling pathway in fungi treated with MeJA.
Key points
• MeJA increased the intracellular level of nitric oxide (NO) in G. lucidum.
• The increase in GA biosynthesis induced by MeJA is activated by NR-generated NO.
• NO acts as a signaling molecule between reactive oxygen species (ROS) and MeJA.
Similar content being viewed by others
References
Ahlawat A, Rana A, Goyal N, Sharma S (2014) Potential role of nitric oxide synthase isoforms in pathophysiology of neuropathic pain. Inflammopharmacology 22(5):269–278
Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357(Pt 3):593–615
Aldridge DC, Galt S, Giles D, Turner WB (1971) Metabolites of Lasiodiplodia theobromae. J Chem Soc C: Organ:1623–1627
Almagro L, Bru R, Pugin A, Pedreno MA (2012) Early signaling network in tobacco cells elicited with methyl jasmonate and cyclodextrins. Plant Physiol Bioch 51:1–9
Ancona-Escalante WD, Baas-Espinola FM, Castro-Concha LA, Vazquez-Flota FA, Zamudio-Maya M, Miranda-Ham MD (2013) Induction of capsaicinoid accumulation in placental tissues of Capsicum chinense Jacq. requires primary ammonia assimilation. Plant Cell Tiss Org 113(3):565–570
Arasimowicz-Jelonek M, Floryszak-Wieczorek J (2016) Nitric oxide in the offensive strategy of fungal and oomycete plant pathogens. Front Plant Sci 7:252
Astuti RI, Nasuno R, Takagi H (2016) Nitric oxide signaling in yeast. Appl Microbiol Biot 100(22):9483–9497
Baidya S, Cary JW, Grayburn WS, Calvo AM (2011) Role of nitric oxide and flavohemoglobin homolog genes in Aspergillus nidulans sexual development and mycotoxin production. Appl Environ Microb 77(15):5524–5528
Berchner-Pfannschmidt U, Tug S, Kirsch M, Fandrey J (2010) Oxygen-sensing under the influence of nitric oxide. Cell Signal 22(3):349–356
Canovas D, Marcos JF, Marcos AT, Strauss J (2016) Nitric oxide in fungi: is there NO light at the end of the tunnel? Curr Genet 62(3):513–518
Cheng CR, Yang M, Yu K, Guan SH, Wu XH, Wu WY, Sun Y, Li C, Ding J, Guo DA (2013a) Metabolite identification of crude extract from Ganoderma lucidum in rats using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. J Chromatogr B 941:90–99
Cheng PG, Phan CW, Sabaratnam V, Abdullah N, Abdulla MA, Kuppusamy UR (2013b) Polysaccharides-rich extract of Ganoderma lucidum (MA Curtis:Fr.) P. Karst accelerates wound healing in Streptozotocin-induced diabetic rats. Evid-Based Compl Alt Med 2013:671252
Chiang KT, Shinyashiki M, Switzer CH, Valentine JS, Gralla EB, Thiele DJ, Fukuto JM (2000) Effects of nitric oxide on the copper-responsive transcription factor Ace1 in Saccharomyces cerevisiae: cytotoxic and cytoprotective actions of nitric oxide. Arch Biochem Biophys 377(2):296–303
Colabardini AC, Brown NA, Savoldi M, Goldman MHS, Goldman GH (2013) Functional characterization of Aspergillus nidulans ypkA, a homologue of the mammalian kinase SGK. PLoS One 8(3):e57630
Conceicao PM, Chaves AFA, Navarro MV, Castilho DG, Calado JCP, Haniu AECJ, Xander P, Batista WL (2019) Cross-talk between the ras GTPase and the Hog1 survival pathways in response to nitrosative stress in Paracoccidioides brasiliensis. Nitric Oxide-Biol Ch 86:1–11
Domitrovic T, Palhano FL, Barja-Fidalgo C, DeFreitas M, Orlando MTD, Fernandes PMB (2003) Role of nitric oxide in the response of Saccharomyces cerevisiae cells to heat shock and high hydrostatic pressure. FEMS Yeast Res 3(4):341–346
Freitas ACN, Silva GC, Pacheco DF, Pimenta AMC, Lemos VS, Duarte IDG, de Lima ME (2017) The synthetic peptide PnPP-19 induces peripheral antinociception via activation of NO/cGMP/K-ATP pathway: role of eNOS and nNOS. Nitric Oxide-Biol Ch 64:31–38
Gong XY, Fu YP, Jiang DH, Li GQ, Yi XH, Peng YL (2007) L-Arginine is essential for conidiation in the filamentous fungus Coniothyrium minitans. Fungal Genet Biol 44(12):1368–1379
Goossens A, Hakkinen ST, Laakso I, Seppanen-Laakso T, Biondi S, De Sutter V, Lammertyn F, Nuutila AM, Soderlund H, Zabeau M, Inze D, Oksman-Caldentey KM (2003) A functional genomics approach toward the understanding of secondary metabolism in plant cells. Proc Natl Acad Sci U S A 100(14):8595–8600
Gorren ACF, Mayer B (2007) Nitric-oxide synthase: a cytochrome P450 family foster child. Bba-Gen Subjects 1770(3):432–445
Gupta KJ, Fernie AR, Kaiser WM, van Dongen JT (2011) On the origins of nitric oxide. Trends Plant Sci 16(3):160–168
Hagen T, Taylor CT, Lam F, Moncada S (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1 alpha. Science 302(5652):1975–1978
Heller J, Tudzynski P (2011) Reactive oxygen species in phytopathogenic fungi: signaling, development, and disease. Annu Rev Phytopathol 49:369–390
Kenne GJ, Gummadidala PM, Omebeyinje MH, Mondal AM, Bett DK, McFadden S, Bromfield S, Banaszek N, Velez-Martinez M, Mitra C, Mikell I, Chatterjee S, Wee J, Chanda A (2018) Activation of aflatoxin biosynthesis alleviates total ROS in Aspergillus parasiticus. Toxins 10(2):57
Khalil ZG, Kalansuriya P, Capon RJ (2014) Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism. Mycology 5(3):168–178
Kojima H, Urano Y, Kikuchi K, Higuchi T, Hirata Y, Nagano T (1999) Fluorescent indicators for imaging nitric oxide production. Angew Chem Int Ed Engl 38(21):3209–3212
Lai T, Chen Y, Li B, Qin G, Tian S (2014) Mechanism of Penicillium expansum in response to exogenous nitric oxide based on proteomics analysis. J Proteome 103:47–56
Leskosek-Cukalovic I, Despotovic S, Lakic N, Niksic M, Nedovic V, Tesevic V (2010) Ganoderma lucidum - medical mushroom as a raw material for beer with enhanced functional properties. Food Res Int 43(9):2262–2269
Li M, Chen T, Gao T, Miao Z, Jiang A, Shi L, Ren A, Zhao M (2015) UDP-glucose pyrophosphorylase influences polysaccharide synthesis, cell wall components, and hyphal branching in Ganoderma lucidum via regulation of the balance between glucose-1-phosphate and UDP-glucose. Fungal Genet Biol 82:251–263
Liu H, Li J, Zhao F, Wang H, Qu Y, Mu D (2015) Nitric oxide synthase in hypoxic or ischemic brain injury. Rev Neurosci 26(1):105–117
Liu R, Shi L, Zhu T, Yang T, Ren A, Zhu J, Zhao MW (2018) Cross-talk between nitric oxide and calcium-calmodulin regulate ganoderic acid biosynthesis in Ganoderma lucidum under heat stress. Appl Environ Microbiol 84(10):e00043–e00018
Lozano-Juste J, Leon J (2010) Enhanced abscisic acid-mediated responses in nia1nia2noa1-2 triple mutant impaired in NIA/NR-and AtNOA1-dependent nitric oxide biosynthesis in Arabidopsis. Plant Physiol 152(2):891–903
Maier J, Hecker R, Rockel P, Ninnemann H (2001) Role of nitric oxide synthase in the light-induced development of sporangiophores in Phycomyces blakesleeanus. Plant Physiol 126(3):1323–1330
Marcos AT, Ramos MS, Marcos JF, Carmona L, Strauss J, Canovas D (2016) Nitric oxide synthesis by nitrate reductase is regulated during development in Aspergillus. Mol Microbiol 99(1):15–33
Meimaroglou DM, Galanopoulou D, Markaki P (2009) Study of the effect of methyl jasmonate concentration on aflatoxin B(1) biosynthesis by Aspergillus parasiticus in yeast extract sucrose medium. Int J Microbiol 2009:842626
Missall TA, Pusateri ME, Donlin MJ, Chambers KT, Corbett JA, Lodge JK (2006) Posttranslational, translational, and transcriptional responses to nitric oxide stress in Cryptococcus neoformans: implications for virulence. Eukaryot Cell 5(3):518–529
Mu D, Li C, Zhang X, Li X, Shi L, Ren A, Zhao M (2014) Functions of the nicotinamide adenine dinucleotide phosphate oxidase family in Ganoderma lucidum: an essential role in ganoderic acid biosynthesis regulation, hyphal branching, fruiting body development, and oxidative-stress resistance. Environ Microbiol 16(6):1709–1728
Mur LAJ, Mandon J, Cristescu SM, Harren FJM, Prats E (2011) Methods of nitric oxide detection in plants: a commentary. Plant Sci 181(5):509–519
Ninnemann H, Maier J (1996) Indications for the occurrence of nitric oxide synthases in fungi and plants and the involvement in photoconidiation of Neurospora crassa. Photochem Photobiol 64(2):393–398
Owayed A, Dhaunsi GS, Al-Mukhaizeem F (2008) Nitric oxide-mediated activation of NADPH oxidase by salbutamol during acute asthma in children. Cell Biochem Funct 26(5):603–608
Rasul S, Dubreuil-Maurizi C, Lamotte O, Koen E, Poinssot B, Alcaraz G, Wendehenne D, Jeandroz S (2012) Nitric oxide production mediates oligogalacturonide-triggered immunity and resistance to Botrytis cinerea in Arabidopsis thaliana. Plant Cell Environ 35(8):1483–1499
Ren A, Qin L, Shi L, Dong X, de Mu S, Li YX, Zhao MW (2010) Methyl jasmonate induces ganoderic acid biosynthesis in the basidiomycetous fungus Ganoderma lucidum. Bioresour Technol 101(17):6785–6790
Ren A, Li MJ, Shi L, Mu DS, Jiang AL, Han Q, Zhao MW (2013) Profiling and quantifying differential gene transcription provide insights into ganoderic acid biosynthesis in Ganoderma lucidum in response to methyl jasmonate. PLoS One 8(6):e65027
Ren A, Liu R, Miao ZG, Zhang X, Cao PF, Chen TX, Li CY, Shi L, Jiang AL, Zhao MW (2017) Hydrogen-rich water regulates effects of ROS balance on morphology, growth and secondary metabolism via glutathione peroxidase in Ganoderma lucidum. Environ Microbiol 19(2):566–583
Rodriguez-Romero J, Hedtke M, Kastner C, Muller S, Fischer R (2010) Fungi, hidden in soil or up in the air: light makes a difference. Annu Rev Microbiol 64:585–610
Rohn TT, Nelson LK, Sipes KM, Swain SD, Jutila KL, Quinn MT (1999) Priming of human neutrophils by peroxynitrite: potential role in enhancement of the local inflammatory response. J Leukoc Biol 65:59–70
Russell R, Paterson M (2006) Ganoderma - a therapeutic fungal biofactory. Phytochemistry 67(18):1985–2001
Saito N, Nakamura Y, Mori IC, Murata Y (2009) Nitric oxide functions in both methyl jasmonate signaling and abscisic acid signaling in Arabidopsis guard cells. Plant Signal Behav 4(2):119–120
Samalova M, Johnson J, Illes M, Kelly S, Fricker M, Gurr S (2013) Nitric oxide generated by the rice blast fungus Magnaporthe oryzae drives plant infection. New Phytol 197(1):207–222
Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS (2009) Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol 10(8):717–742
Santolini J, Andre F, Jeandroz S, Wendehenne D (2017) Nitric oxide synthase in plants: where do we stand? Nitric Oxide-Biol Ch 63:30–38
Sarkar TS, Biswas P, Ghosh SK, Ghosh S (2014) Nitric oxide production by necrotrophic pathogen Macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions. PLoS One 9(9):e107348
Scheler C, Durner J, Astier J (2013) Nitric oxide and reactive oxygen species in plant biotic interactions. Curr Opin Plant Biol 16(4):534–539
Shi L, Gong L, Zhang X, Ren A, Gao T, Zhao M (2015) The regulation of methyl jasmonate on hyphal branching and GA biosynthesis in Ganoderma lucidum partly via ROS generated by NADPH oxidase. Fungal Genet Biol 81:201–211
Sliva D, Loganathan J, Jiang J, Jedinak A, Lamb JG, Terry C, Baldridge LA, Adamec J, Sandusky GE, Dudhgaonkar S (2012) Mushroom Ganoderma lucidum prevents colitis-associated carcinogenesis in mice. PLoS One 7(10):e47873
Song NK, Jeong CS, Choi HS (2000) Identification of nitric oxide synthase in Flammulina velutipes. Mycologia 92(6):1027–1032
Suarez-Arroyo IJ, Rosario-Acevedo R, Aguilar-Perez A, Clemente PL, Cubano LA, Serrano J, Schneider RJ, Martinez-Montemayor MM (2013) Anti-tumor effects of Ganoderma lucidum (reishi) in inflammatory breast cancer in in vivo and in vitro models. PLoS One 8(2):e57431
Tain YL, Hsu CN (2016) Targeting on asymmetric dimethylarginine-related nitric oxide-reactive oxygen species imbalance to reprogram the development of hypertension. Int J Mol Sci 17(12):2020
Vandelle E, Delledonne M (2011) Peroxynitrite formation and function in plants. Plant Sci 181(5):534–539
Wang H, Ng TB (2006) Ganodermin, an antifungal protein from fruiting bodies of the medicinal mushroom Ganoderma lucidum. Peptides 27(1):27–30
Wang JW, Wu JY (2005) Nitric oxide is involved in methyl jasmonate-induced defense responses and secondary metabolism activities of Taxus cells. Plant Cell Physiol 46(6):923–930
Wasternack C, Hause B (2013) Jasmonates: biosynthesis, perception, signal transduction and action in plant stress response, growth and development. An update to the 2007 review in Annals of Botany. Ann Bot 111(6):1021–1058
Wu XY, Ding CH, Baerson SR, Lian FZ, Lin XH, Zhang LQ, Wu CF, Hwang SY, Zeng RS, Song YY (2019) The roles of jasmonate signalling in nitrogen uptake and allocation in rice (Oryza sativa L.). Plant Cell Environ 42(2):659–672
Xie YJ, Mao Y, Zhang W, Lai DW, Wang QY, Shen WB (2014) Reactive oxygen species-dependent nitric oxide production contributes to hydrogen-promoted stomatal closure in Arabidopsis. Plant Physiol 165(2):759–773
Yang SL, Chung KR (2012) The NADPH oxidase-mediated production of hydrogen peroxide (H(2)O(2)) and resistance to oxidative stress in the necrotrophic pathogen Alternaria alternata of citrus. Mol Plant Pathol 13(8):900–914
Yin SN, Gao ZJ, Wang CF, Huang LL, Kang ZS, Zhang HC (2016) Nitric oxide and reactive oxygen species coordinately regulate the germination of Puccinia striiformis f. sp tritici Urediniospores. Front Microbiol 7:178
Yu Y, Yang ZJ, Guo K, Li Z, Zhou HZ, Wei YL, Li JS, Zhang XJ, Harvey P, Yang HT (2015) Oxidative damage induced by heat stress could be relieved by nitric oxide in Trichoderma harzianum LTR-2. Curr Microbiol 70(4):618–622
Yun BW, Feechan A, Yin MH, Saidi NBB, Le Bihan T, Yu M, Moore JW, Kang JG, Kwon E, Spoel SH, Pallas JA, Loake GJ (2011) S-nitrosylation of NADPH oxidase regulates cell death in plant immunity. Nature 478(7368):264–268
Zea AH, Aiyar A, Tate D (2014) Dual effect of interferon (IFN gamma)-induced nitric oxide on tumorigenesis and intracellular bacteria. Vitam Horm 96:299–321
Zhang Y, Zhu H, Zhang Q, Li M, Yan M, Wang R, Wang L, Welti R, Zhang W, Wang X (2009) Phospholipase dalpha1 and phosphatidic acid regulate NADPH oxidase activity and production of reactive oxygen species in ABA-mediated stomatal closure in Arabidopsis. Plant Cell 21(8):2357–2377
Zhao MG, Chen L, Zhang LL, Zhang WH (2009) Nitric reductase-dependent nitric oxide production is involved in cold acclimation and freezing tolerance in Arabidopsis. Plant Physiol 151(2):755–767
Zhao YX, Xi Q, Xu Q, He MH, Ding JN, Dai YC, Keller NP, Zheng WF (2015) Correlation of nitric oxide produced by an inducible nitric oxide synthase-like protein with enhanced expression of the phenylpropanoid pathway in Inonotus obliquus cocultured with Phellinus morii. Appl Microbiol Biot 99(10):4361–4372
Zheng WF, Mao KJ, Zhang YX, Pan SY, Zhang MM, Jiang H (2009) Nitric oxide mediates the fungal-elicitor-enhanced biosynthesis of antioxidant polyphenols in submerged cultures of Inonotus obliquus. Microbiol-SGM 155:3440–3448
Funding
This work was financially supported by the Fundamental Research Funds for the Central Universities (Project No. KYZ201860), the National Natural Science Foundation of China (Project No. 31672212; 31972059), the earmarked fund for the China Agriculture Research System (Project No. CARS-20), the Key Research and Development Program of Jiangsu Province (Project No. BE2019385), and the China Postdoctoral Science Foundation (Project No. 2016M590468).
Author information
Authors and Affiliations
Contributions
LS and MWZ conceived and designed the research. LS, SNY, and TG conducted the experiments. LS, JZ, AR, HSY, HW, and MWZ analyzed the data and revised the manuscript. LS wrote the manuscript. All authors read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflicts of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 1180 kb)
Rights and permissions
About this article
Cite this article
Shi, L., Yue, S., Gao, T. et al. Nitrate reductase-dependent nitric oxide plays a key role on MeJA-induced ganoderic acid biosynthesis in Ganoderma lucidum. Appl Microbiol Biotechnol 104, 10737–10753 (2020). https://doi.org/10.1007/s00253-020-10951-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-020-10951-y