title: "Self" and "non-self" in the control of phytoalexin biosynthesis: plant phospholipases A2 with alkaloid-specific molecular fingerprints.
abstract: The overproduction of specialized metabolites requires plants to manage the inherent burdens, including the risk of self-intoxication. We present a control mechanism that stops the expression of phytoalexin biosynthetic enzymes by blocking the antecedent signal transduction cascade. Cultured cells of Eschscholzia californica (Papaveraceae) and Catharanthus roseus (Apocynaceae) overproduce benzophenanthridine alkaloids and monoterpenoid indole alkaloids, respectively, in response to microbial elicitors. In both plants, an elicitor-responsive phospholipase A2 (PLA2) at the plasma membrane generates signal molecules that initiate the induction of biosynthetic enzymes. The final alkaloids produced in the respective plant inhibit the respective PLA, a negative feedback that prevents continuous overexpression. The selective inhibition by alkaloids from the class produced in the "self" plant could be transferred to leaves of Nicotiana benthamiana via recombinant expression of PLA2. The 3D homology model of each PLA2 displays a binding pocket that specifically accommodates alkaloids of the class produced by the same plant, but not of the other class; for example, C. roseus PLA2 only accommodates C. roseus alkaloids. The interaction energies of docked alkaloids correlate with their selective inhibition of PLA2 activity. The existence in two evolutionary distant plants of phospholipases A2 that discriminate "self-made" from "foreign" alkaloids reveals molecular fingerprints left in signal enzymes during the evolution of species-specific, cytotoxic phytoalexins.
authors: Institute of Pharmacy, Department of Pharmaceutical Biology, Lab of Molecular Cell Biology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany.
authors: Michael
authors: M
authors: Heinze
authors: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, 06120 Halle (Saale), Germany.
authors: Wolfgang
authors: W
authors: Brandt
authors: Department of Metabolic Cell Biology, Leibniz Institute of Plant Biochemistry, 06120 Halle (Saale), Germany.
authors: Sylvestre
authors: S
authors: Marillonnet
authors: Institute of Pharmacy, Department of Pharmaceutical Biology, Lab of Molecular Cell Biology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany werner.roos@pharmazie.uni-halle.de.
authors: Werner
authors: W
authors: Roos
mesh_terms: D000470:Alkaloids / Q000378:metabolism*; D000595:Amino Acid Sequence; D053119:Benzophenanthridines / Q000494:pharmacology; D001665:Binding Sites; D053898:Biosynthetic Pathways / Q000187:drug effects; D030008:Catharanthus / Q000187:drug effects / Q000201:enzymology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003001:Cloning, Molecular; D020868:Gene Silencing / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D028101:Papaveraceae / Q000166:cytology / Q000187:drug effects; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D012717:Sesquiterpenes / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000094162:Phytoalexins
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D007546:Isoquinolines; D012717:Sesquiterpenes; C005705:sanguinarine; D054467:Phospholipases A2; D000094162:Phytoalexins