Distinct Mechanisms of Biotic and Chemical Elicitors Enable Additive Elicitation of the Anticancer Phytoalexin Glyceollin I

Phytoalexins are metabolites biosynthesized in plants in response to pathogen, environmental, and chemical stresses that often have potent bioactivities, rendering them promising for use as therapeutics or scaffolds for pharmaceutical development. Glyceollin I is an isoflavonoid phytoalexin from soybean that exhibits potent anticancer activities and is not economical to synthesize. Here, we tested a range of source tissues from soybean, in addition to chemical and biotic elicitors, to understand how to enhance the bioproduction of glyceollin I. Combining the inorganic chemical silver nitrate (AgNO3) with the wall glucan elicitor (WGE) from the soybean pathogen Phytophthora sojae had an additive effect on the elicitation of soybean seeds, resulting in a yield of up to 745.1 µg gt−1 glyceollin I. The additive elicitation suggested that the biotic and chemical elicitors acted largely by separate mechanisms. WGE caused a major accumulation of phytoalexin gene transcripts, whereas AgNO3 inhibited and enhanced the degradation of glyceollin I and 6″-O-malonyldaidzin, respectively.

[1]  C. Selvam,et al.  Pterocarpan scaffold: A natural lead molecule with diverse pharmacological properties. , 2017, European journal of medicinal chemistry.

[2]  J. Vincken,et al.  Glyceollins and dehydroglyceollins isolated from soybean act as SERMs and ER subtype-selective phytoestrogens , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[3]  H. Takatsuji,et al.  Diterpenoid phytoalexin factor, a bHLH transcription factor, plays a central role in the biosynthesis of diterpenoid phytoalexins in rice. , 2015, The Plant journal : for cell and molecular biology.

[4]  Qun Cheng,et al.  Overexpression of Soybean Isoflavone Reductase (GmIFR) Enhances Resistance to Phytophthora sojae in Soybean , 2015, Front. Plant Sci..

[5]  Robert J. Schmitz,et al.  Targeted genome modifications in soybean with CRISPR/Cas9 , 2015, BMC Biotechnology.

[6]  C. Shyu,et al.  A Sorghum MYB Transcription Factor Induces 3-Deoxyanthocyanidins and Enhances Resistance against Leaf Blights in Maize , 2015, Molecules.

[7]  T. Eulgem,et al.  Synthetic plant defense elicitors , 2015, Front. Plant Sci..

[8]  C. Hébrard,et al.  Deciphering the Role of Phytoalexins in Plant-Microorganism Interactions and Human Health , 2014, Molecules.

[9]  G. Hartman,et al.  Glyceollin is an important component of soybean plant defense against Phytophthora sojae and Macrophomina phaseolina. , 2013, Phytopathology.

[10]  J. Vincken,et al.  Modulation of isoflavonoid composition of Rhizopus oryzae elicited soybean (Glycine max) seedlings by light and wounding. , 2013, Journal of agricultural and food chemistry.

[11]  Dominik K. Grosskinsky,et al.  Phytoalexin transgenics in crop protection--fairy tale with a happy end? , 2012, Plant science : an international journal of experimental plant biology.

[12]  A. Bones,et al.  Phytoalexins in defense against pathogens. , 2012, Trends in plant science.

[13]  L. Rhodes,et al.  Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer. , 2012, Oncology letters.

[14]  B. Miki,et al.  Combined analysis of transcriptome and metabolite data reveals extensive differences between black and brown nearly-isogenic soybean (Glycine max) seed coats enabling the identification of pigment isogenes , 2011, BMC Genomics.

[15]  Amarjit Luniwal,et al.  Multigram Synthesis of Glyceollin I , 2011 .

[16]  J. Vincken,et al.  Increasing soy isoflavonoid content and diversity by simultaneous malting and challenging by a fungus to modulate estrogenicity. , 2011, Journal of agricultural and food chemistry.

[17]  J. Vincken,et al.  Identification of prenylated pterocarpans and other isoflavonoids in Rhizopus spp. elicited soya bean seedlings by electrospray ionisation mass spectrometry. , 2011, Rapid communications in mass spectrometry : RCM.

[18]  M. Lacey,et al.  Glyceollin I, a Novel Antiestrogenic Phytoalexin Isolated from Activated Soy , 2010, Journal of Pharmacology and Experimental Therapeutics.

[19]  Kanako Sasaki,et al.  Molecular Cloning and Characterization of a cDNA for Pterocarpan 4-Dimethylallyltransferase Catalyzing the Key Prenylation Step in the Biosynthesis of Glyceollin, a Soybean Phytoalexin1[W] , 2008, Plant Physiology.

[20]  R. Dixon,et al.  Different mechanisms for phytoalexin induction by pathogen and wound signals in Medicago truncatula , 2007, Proceedings of the National Academy of Sciences.

[21]  M. Gijzen,et al.  Patterns of gene expression upon infection of soybean plants by Phytophthora sojae. , 2004, Molecular plant-microbe interactions : MPMI.

[22]  Jia-Wei Wang,et al.  Characterization of GaWRKY1, a Cotton Transcription Factor That Regulates the Sesquiterpene Synthase Gene (+)-δ-Cadinene Synthase-A1 , 2004, Plant Physiology.

[23]  Lloyd W Sumner,et al.  Regiospecific hydroxylation of isoflavones by cytochrome p450 81E enzymes from Medicago truncatula. , 2003, The Plant journal : for cell and molecular biology.

[24]  T. Cleveland,et al.  Phytochemical Glyceollins, Isolated from Soy, Mediate Antihormonal Effects through Estrogen Receptor α and β1 , 2001 .

[25]  T. Cleveland,et al.  Phytochemical glyceollins, isolated from soy, mediate antihormonal effects through estrogen receptor alpha and beta. , 2001, The Journal of clinical endocrinology and metabolism.

[26]  T. Cleveland,et al.  Induction of the soybean phytoalexins coumestrol and glyceollin by Aspergillus. , 2000, Journal of agricultural and food chemistry.

[27]  T. L. Graham,et al.  Signaling in Soybean Phenylpropanoid Responses (Dissection of Primary, Secondary, and Conditioning Effects of Light, Wounding, and Elicitor Treatments) , 1996, Plant physiology.

[28]  T. L. Graham,et al.  Flavonoid and isoflavonoid distribution in developing soybean seedling tissues and in seed and root exudates. , 1991, Plant physiology.

[29]  M. Bhattacharyya,et al.  Abscisic Acid Suppression of Phenylalanine Ammonia-Lyase Activity and mRNA, and Resistance of Soybeans to Phytophthora megasperma f.sp. glycinea. , 1989, Plant physiology.

[30]  M. Bhattacharyya,et al.  Resistance, susceptibility and accumulation of glyceollins I–III in soybean organs inoculated with Phytophthora megasperma f. sp. glycinea , 1986 .

[31]  M. Bhattacharyya,et al.  Expression of gene-specific and age-related resistance and the accumulation of glyceollin in soybean leaves infected with Phytophthora megasperma f. sp. glycinea , 1986 .

[32]  E. Elstner,et al.  Ethylene: indicator but not inducer of phytoalexin synthesis in soybean. , 1980, Plant physiology.

[33]  M. Yoshikawa.  Diverse modes of action of biotic and abiotic phytoalexin elicitors , 1978, Nature.

[34]  E. Beyer.  A potent inhibitor of ethylene action in plants. , 1976, Plant physiology.

[35]  F. Finelli,et al.  Host-Pathogen Interactions: IX. Quantitative Assays of Elicitor Activity and Characterization of the Elicitor Present in the Extracellular Medium of Cultures of Phytophthora megasperma var. sojae. , 1976, Plant physiology.

[36]  P. Albersheim,et al.  Host-Pathogen Interactions: X. Fractionation and Biological Activity of an Elicitor Isolated from the Mycelial Walls of Phytophthora megasperma var. sojae. , 1976, Plant physiology.

[37]  F. Finelli,et al.  IX. QUANTITATIVE ASSAYS OF ELICITOR ACTIVITY AND CHARACTERIZATION OF THE ELICITOR PRESENT IN THE EXTRACELLULAR MEDIUM OF CULTURES OF PHYTOPHTHORA MEGA- SPERMA VAR. SOJAE' , 1976 .