|Pan, Zhiqiang - Peter|
Submitted to: Plant Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2008
Publication Date: 5/8/2008
Citation: Dayan, F.E., Ferriera, D., Wang, Y., Khan, I.A., Mcinroy, J.A., Pan, Z. 2008. A pathogenic fungi diphenyl ether phytotoxin targets plant enoyl (acyl carrier protein) reductase. Plant Physiology. 147:1062-1071.
Interpretive Summary: The biochemical interactions between pathogenic microorganisms and their host plants are very intricate, often resulting from a dynamic and continually evolving process. Cyperin is a natural phytotoxic diphenyl ether released by several fungal pathogens as they invade plants. This natural product causes membranes to leak and leads to cell death. We report that cyperin inhibits the enzyme enoyl (acyl carrier protein) reductase (ENR). The binding of cyperin in ENR involves an interaction with an important cofactor (NAD). Therefore, cyperin may contribute to the virulence of the pathogens by inhibiting ENR and destabilizing the membrane integrity of the cells surrounding the point of infection.
Technical Abstract: Cyperin is a natural phytotoxic diphenyl ether produced by several fungal plant pathogens. At high concentrations, this metabolite inhibits protoporphyrinogen oxidase, a key enzyme in porphyrin synthesis. However, unlike its herbicide structural analogues, the mode of action of cyperin is not light-dependent, causing loss of membrane integrity in the dark. We report that this natural diphenyl ether inhibits Arabidopsis thaliana enoyl (acyl carrier protein) reductase (ENR). This enzyme is also sensitive to triclosan, a synthetic antimicrobial diphenyl ether. While cyperin was much less potent than triclosan on this target site, their ability to cause light-independent disruption of membrane integrity and inhibition of ENR are similar at their respective phytotoxic concentrations. The sequence of ENR is highly conserved within higher plants and a homology model of A. thaliana ENR was derived from the crystal structure of the protein from Brassica napus. Cyperin mimicked the binding of triclosan in the binding pocket of ENR. Both molecules were stabilized by the Pi-Pi stacking interaction between one of their phenyl rings and the nicotinamide ring of the NAD+. Furthermore, the side chain of tyrosine is involved in hydrogen bonding with a phenolic hydroxy group of cyperin. Therefore, cyperin may contribute to the virulence of the pathogens by inhibiting ENR and destabilizing the membrane integrity of the cells surrounding the point of infection.