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Molecules 2015, 20(2), 2770-2774; doi:10.3390/molecules20022770

Editorial
Phytoalexins: Current Progress and Future Prospects
Laboratory of Stress, Defenses and Plant Reproduction, Research Unit "Vines and Wines of Champagne", UPRES EA 4707, Department of Biology and Biochemistry, Faculty of Sciences, University of Reims, P.O. Box 1039, 51687 Reims cedex 02, France
Academic Editor: Derek McPhee
Received: 2 February 2015 / Accepted: 4 February 2015 / Published: 5 February 2015
Phytoalexins are low molecular weight antimicrobial compounds that are produced by plants as a response to biotic and abiotic stresses. As such they take part in an intricate defense system which enables plants to control invading microorganisms. In the 1950s, research on phytoalexins started with progress in their biochemistry and bio-organic chemistry, resulting in the determination of their structure, their biological activity, as well as mechanisms of their synthesis and catabolism by microorganisms. Elucidation of the biosynthesis of numerous phytoalexins also permitted the use of molecular biology tools for the exploration of the genes encoding enzymes of their synthesis pathways and their regulators. This has led to potential applications for increasing plant resistance to diseases. Phytoalexins display an enormous diversity belonging to various chemical families such as for instance, phenolics, terpenoids, furanoacetylenes, steroid glycoalkaloids, sulfur-containing compounds and indoles.
Research and review papers dealing with numerous aspects of phytoalexins including modulation of their biosynthesis, molecular engineering in plants, biological activities, structure/activity relationships and phytoalexin metabolism by micro-organisms are published in this issue.
In the first paper of this special issue on phytoalexins, Jeandet et al. present an overview of this diverse group of molecules, namely their chemical diversity, the main biosynthetic pathways and their regulatory mechanisms, fungal metabolism, phytoalexin gene transfer in plants and their role as antifungal and bactericidal agents as well as their involvement in human health [1].
General aspects of phytoalexins from the Leguminosae and Poaceae families are also discussed in this issue. Phytoalexins from sorghum and maize are presented in details by Poloni and Schirawski [2]. Sorghum produces two distinct phytoalexins belonging to the 3-deoxyanthocyanidin chemical group, apigeninidin and luteolinidin. Their biosynthetic pathways start from the flavanone naringenin according to a scheme slightly different from that of the anthocyanin route. In maize, phytoalexins are represented by members of the terpenoid class, including zealexins and kauralexins on the one hand and benzoxazinoids on the other hand, the biosynthesis of which are fully described. Biosynthesis aspects have been linked to both the elicitation and the up-regulation mechanisms of those phytoalexins. Various applications of sorghum and maize phytoalexins in plant disease resistance and health and biomedicine are also presented.
Within the Leguminosae family, the genus Tephrosia, a large pantropical genus composed of more than 350 species, is a source of numerous chemical constituents possessing various biological properties, including phytoalexin-like compounds. These compounds which are reviewed in this issue by Chen et al., are mainly polyphenolics (flavones, flavonols, flavononols, flavans, isoflavones and chalcones), triterpenoids and sesquiterpenes [3]. Biosynthetic pathways of a number of these compounds are described as well as some of their biological activities as estrogenic, antitumor, antimicrobial, antiprotozoal and antifeedant agents.
Elucidating the molecular mechanisms of the modulation of phytoalexin biosynthesis finds applications in plant engineering for disease resistance. In this issue, Formela et al. report the effects of various sugars (sucrose, glucose and fructose) acting as endogenous signals on the mechanisms regulating the biosynthesis and accumulation of the lupine phytoalexin, genistein as well as the expression of other isoflavonoid biosynthetic genes [4]. Zernova et al. describe the transformation of soybean hairy roots with both the peanut resveratrol synthase 3 AhRS3 gene and the resveratrol-O-methyltransferase ROMT gene [5]. Overexpression of these two genes resulted in the production of resveratrol and its methylated derivative pterostilbene and a lower necrosis of the transformed tissues (only 0 to 7%) in response to the soybean pathogen Rhizoctonia solani compared to the wild-type ones which exhibited about 84% necrosis. Biosynthesis of the 3-deoxyanthocyanidin phytoalexins from sorghum is reported in transgenic maize lines expressing the MYB transcription factor yellow seed1 (y1), an orthologue of the maize gene pericarp color1 (p1) in the work of Ibraheem et al. [6]. Expression of this transcription factor leads to the production of chemically modified 3-deoxyanthocyanidins and a resistance response of Y1-maize plants to leaf blight (Colletotrichum graminicola).
It is well known that treatment of plants with various biotic or abiotic agents, the so-called elicitors, can activate complex mechanisms in the cells by altering primary and secondary metabolisms in a coordinate fashion. Elicitors are also recognized as efficient inducers of phytoalexins. In this issue, Hadwiger and Tanaka report that EDTA, used at low concentrations, is a new elicitor of pisatin, a phytoalexin indicator of non-host resistance in pea [7]. Eliciting activity of EDTA seems to be linked to induction of cell DNA damage and defense-responsive genes.
The question of the function of phytoalexins as true antifungal agents still remains unanswered. Interestingly, a study of Sanzani et al. underline the effectiveness both in vitro and in vivo of some polyphenolic phytoalexins, namely the coumarin, scopoletin, on the reduction of green mold symptoms caused by Penicillium digitatum on oranges by 40 to 85% [8]. Based on these results, the authors conclude that treatment of plants with phytoalexins may represent an interesting alternative to synthetic fungicides. In another work by Hasegawa et al., the activity of two rice phytoalexins, sakuranetin and momilactone A was tested in vitro and in vivo on the blast fungus Magnaporthe oryzae. Sakuranetin exhibits a higher antifungal activity than does momilactone A, respectively 40%–55% and 12%–17% reduction of mycelial growth [9].
To increase the fungitoxicity of phytoalexins, design and synthesis of more active phytoalexin derivatives is needed. Chalal et al. report in this issue the synthesis of a series of 13 trans-resveratrol analogues via Wittig or Heck reactions and assess their antimicrobial activity on two different grapevine pathogens, Plasmopara viticola and Botrytis cinerea [10]. Stilbenes displayed a spectrum of activity ranging from low to high, suggesting a relationship between the chemical structures of the synthesized stilbenes (number and position of methoxy and hydroxyphenyl groups) and their antimicrobial activity.
The ability of a fungal pathogen to weaken or neutralize the toxic effects of phytoalexins is one of the essential parameters determining the outcome of the interaction between this pathogen and its host plant. The necrotrophic fungus Alternaria brassicicola is known to detoxify brassinin, the indolic phytoalexin from the Brassicaceae family. A transcription factor Bdtf1 is essential for brassinin detoxification and fungal host range. In this issue, Cho et al. show that beside this transcriptional factor, 10 putative genes were assumed to be involved in the detoxification of brassinin using a Bdtf1-deletion mutant of the necrotrophic fungus A. brassicicola [11].
Another limitation in our knowledge of phytoalexins is the difficulty in analyzing the events occurring between the plant and the pathogen under natural conditions. Some attempts to determine the actual concentrations and the nature of phytoalexins directly in plant tissues in response to invading microorganisms have been carried out using spectroscopic methods. Becker et al. in this issue describe mass spectrometry (ESI-FTIR-RMS) and imaging mass spectrometry techniques to evaluate the response of grapevine leaves to P. viticola, the causal agent of downy mildew [12]. Most importantly, molecular mapping of grapevine leaves by laser desorption/ionization mass spectrometry reveals a specific spatial distribution of some stilbene phytoalexins produced upon the infection process. To assess modifications of the phytoalexin metabolism in planta, global and untargeted approaches are also needed. Here, Marti et al. use a Liquid Chromatography-High Resolution Mass Spectrometry-based metabolomic approach to evaluate stilbene phytoalexin modifications as a response to an abiotic stress (UV-C radiations) in leaves of three different model plant species, Cissus Antarctica Vent. (Vitaceae), Vitis vinifera L. (Vitaceae) and Cannabis sativa L. (Cannabaceae) [13].
Interestingly, phytoalexins have found many applications in human health and disease. For example, Lozano-Mena et al. review in this issue the role of maslinic acid, a pentacyclic triterpene phytoalexin-like compound present in various natural sources such as herbal remedies as well as edible vegetables and fruits, as an antitumor, antidiabetic, antioxidant, cardioprotective, neuroprotective, antiparasitic and growth-stimulating agent both in experimental and animal models [14]. This offers perspectives for this compound to be used as a nutraceutical. Moreover, other phytoalexins such as brassinin and its derivative, homobrassinin, show marked antiproliferative activities in vitro. In this issue, Kello et al. indeed report that the inhibitory effects of the phytoalexin homobrassinin in human colorectal cancer cells is associated with apoptosis, G2/M phase arrest, deregulation of tubulin expression together with the loss of mitochondrial membrane potential, caspase-3 activation and intracellular reactive oxygen species production [15]. Smith et al. also demonstrate that the indolic phytoalexin, camalexin, exerts antitumor activity against prostate cancer cell lines by alterations of expression and activity of a lysosomal protease, cathepsin D [16]. Immunochemical analysis reveals cathepsin D relocalization from the lysosome to the cytoplasm according to camalexin treatment which is responsible for apoptosis in those cells. One of the most promising molecules in terms of biological benefits for humans, the resveratrol, is reviewed by McCalley et al. regarding its effects on intracellular calcium signaling mechanisms [17]. Resveratrol’s mechanisms of action are likely to be pleitropic and mediated by the interaction of this compound with key signaling proteins controlling cellular calcium homeostasis. The clinical relevance of resveratrol actions on excitable cells, transformed or cancer cells and immune cells was put in parallel with the molecular mechanisms affecting intra cellular calcium signaling proteins.
Lack of efficacy of some natural phytoalexins in reducing tumors has led to a number of investigations regarding the design and synthesis of more potent anticancer derivatives of known phytoalexins. Chalal et al. in this issue describe the synthesis of hydroxylated and methylated resveratrol derivatives using Wittig and Heck reactions as well as of ferrocenyl-stilbene analogs, with potent anticancer activities on human colorectal tumor SW480 cell lines [18]. However, weaker effects of the synthesized resveratrol derivatives were observed on the human hepatoblastoma HepG2 cells, showing the selectivity of those compounds for cancer treatment.
All the papers presented in this special issue thus underline the central role of phytoalexins in plant diseases as well as their involvement in human health and disease.

Acknowledgments

The Guest Editor thanks all the authors for their contributions to this special issue, all the reviewers for their work in evaluating the submitted articles and the editorial staff of Molecules, especially Jessica Bai, Jiahua Zhang and Wei Zhang, Assistant Editors of this journal for their kind help in making this special issue.

References

  1. Jeandet, P.; Hébrard, C.; Deville, M.A.; Cordelier, S.; Dorey, S.; Aziz, A.; Crouzet, J. Deciphering the role of phytoalexins in plant-microorganism interactions and human health. Molecules 2014, 19, 18033–18056. [Google Scholar] [CrossRef] [PubMed]
  2. Poloni, A.; Schirawski, J. Red card for pathogens: Phytoalexins in sorghum and maize. Molecules 2014, 19, 9114–9133. [Google Scholar] [CrossRef] [PubMed][Green Version]
  3. Chen, Y.; Tao, Y.; Gao, C.; Cao, W.; Huang, R. Natural products from the genus Tephrosia. Molecules 2014, 19, 1432–1458. [Google Scholar] [CrossRef] [PubMed]
  4. Formela, M.; Samardakiewicz, S.; Marczak, L.; Nowak, W.; Narozna, D.; Waldemar, B.; Kasprowicz-Maluski, A.; Morkunas, I. Effects of endogenous signals and Fusarium oxysporum on the mechanism regulating genistein synthesis and accumulation in yellow lupine and their impact on plant cell cytoskeleton. Molecules 2014, 19, 13392–13421. [Google Scholar] [CrossRef] [PubMed]
  5. Zernova, O.V.; Lygin, A.V.; Pawlowski, M.L.; Hill, C.B.; Hartman, G.L.; Widholm, J.M.; Lozovaya, V.V. Regulation of plant immunity through modulation of phytoalexin synthesis. Molecules 2014, 19, 7480–7496. [Google Scholar] [CrossRef] [PubMed]
  6. Ibraheem, F.; Gaffoor, I.; Sharma, M.; Shyu, C.R.; Chopra, S. A sorghum MYB transcription factor induces 3-deoxyanthocyanidins and enhances resistance against leaf blights in maize. Molecules 2015, 20, 2388–2404. [Google Scholar] [CrossRef] [PubMed]
  7. Hadwiger, L.A.; Tanaka, K. EDTA, a novel inducer of pisatin, a phytoalexin indicator of the non-host resistance in peas. Molecules 2015, 20, 24–34. [Google Scholar] [CrossRef]
  8. Sanzani, S.; Schena, L.; Ippolito, A. Effectiveness of phenolic compounds against citrus green mould. Molecules 2014, 19, 12500–12508. [Google Scholar] [CrossRef] [PubMed]
  9. Hasegawa, M.; Mitsuhara, I.; Seo, S.; Okada, K.; Yamane, H.; Iwai, T.; Ohashi, Y. Analysis on blast fungus-responsive characters of a flavonoid phytoalexin sakuranetin; Accumulation in infected rice leaves, antifungal activity and detoxification by fungus. Molecules 2014, 19, 11404–11418. [Google Scholar] [CrossRef] [PubMed]
  10. Chalal, M.; Klinguer, A.; Echairi, A.; Meunier, P.; Vervandier-Fasseur, D.; Adrian, M. Antimicrobial activity of resveratrol analogues. Molecules 2014, 19, 7679–7688. [Google Scholar] [CrossRef] [PubMed]
  11. Cho, Y.; Ohm, R.A.; Devappa, R.; Lee, H.B.; Grigoriev, I.V.; Kim, B.Y.; Ahn, J.S. Transcriptional responses of the bdtf1-deletion mutant to the phytoalexin brassinin in the necrotrophic fungus Alternaria brassicicola. Molecules 2014, 19, 10717–10732. [Google Scholar] [CrossRef] [PubMed]
  12. Becker, L.; Carré, V.; Poutaraud, A.; Merdinoglu, D.; Chaimbault, P. MALDI mass spectrometry imaging for the simultaneous location of resveratrol, pterostilbene and viniferins on grapevine leaves. Molecules 2014, 19, 10587–10600. [Google Scholar] [CrossRef] [PubMed]
  13. Marti, G.; Schnee, S.; Andrey, Y.; Simoes-Pires, C.; Carrupt, P.A.; Wolfender, J.L.; Gindro, K. Study of leaf metabolome modifications induced by UV-C radiations in representative Vitis, Cissus and Cannabis species by LC-MS based metabolomics and antioxidant assays. Molecules 2014, 19, 14004–14021. [Google Scholar] [CrossRef] [PubMed]
  14. Lozano-Mena, G.; Sanchez-Gonzalez, M.; Juan, M.E.; Planas, J.M. Maslinic acid, a natural phytoalexin-type triterpene from olives—A promising nutraceutical? Molecules 2014, 19, 11538–11559. [Google Scholar] [CrossRef] [PubMed]
  15. Kello, M.; Drutovic, D.; Chripkova, M.; Pilatova, M.; Budovska, L.; Kulikova, L.; Urdzik, P.; Mojzis, J. ROS-dependent antiproliferative effect of brassinin derivative homobrassinin in human colorectal cancer Caco2 cells. Molecules 2014, 19, 10877–10897. [Google Scholar] [CrossRef] [PubMed]
  16. Smith, B.; Randle, D.; Mezencev, R.; Thomas, L.; Hinton, C.; Odero-Marah, V. Camalexin-induced apoptosis in prostate cancer cells involves alterations of expression and activity of lysosomal protease cathepsin D. Molecules 2014, 19, 3988–4005. [Google Scholar] [CrossRef] [PubMed]
  17. McCalley, A.E.; Kaja, S.; Payne, A.J.; Koulen, P. Resveratrol and calcium signaling: molecular mechanisms and clinical relevance. Molecules 2014, 19, 7327–7340. [Google Scholar] [CrossRef] [PubMed]
  18. Chalal, M.; Delmas, D.; Meunier, P.; Latruffe, N.; Vervandier-Fasseur, D. Inhibition of cancer derived cell lines proliferation by synthesized hydroxylated stilbenes and new ferrocenyl-stilbene analogs. Comparison with resveratrol. Molecules 2014, 19, 7850–7868. [Google Scholar] [CrossRef] [PubMed]
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