Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones display activity as cytotoxic phytoalexins and transcriptional mediators

Authors: Christensen, Shawn; Huffaker, Alisa; Kaplan, Fatma; Sims, James; ZIEMANN, SEBASTIAN - University Of Cologne; DOEHLEMANN, GUNTHER - University Of Cologne; JI, LEXIANG - University Of Georgia; SCHMITZ, ROBERT - University Of Georgia; KOLOMIETS, MICHAEL - Texas A&M University; Alborn, Hans; MORI, NAOKI - Kyoto University; JANDER, GEORG - Boyce Thompson Institute; Ni, Xinzhi; SARTOR, RYAN - University Of California; Byers, Sara; Abdo, Zaid; Schmelz, Eric

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/27/2015
Publication Date: 9/8/2015
Citation: Christensen, S.A., Huffaker, A., Kaplan, F., Sims, J.W., Ziemann, S., Doehlemann, G., Ji, L., Schmitz, R.J., Kolomiets, M.V., Alborn, H.T., Mori, N., Jander, G., Ni, X., Sartor, R.C., Byers, S.O., Abdo, Z., Schmelz, E.A. 2015. Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones display activity as cytotoxic phytoalexins and transcriptional mediators. Proceedings of the National Academy of Sciences. 112(36):11407-11412.

Interpretive Summary: Dramatic and harmful forms of disease in crops are countered by small molecules that mediate defense. In plants, 12-oxo-phytodienoic acid and jasmonic acid, termed jasmonates, are key linolenate oxidation products generated by the 13-lipoxygenase pathway that regulate innate immune responses. A less well-known yet conceptually parallel metabolic pathway branch is generated by 9-lipoxygenase activity on linoleic acid, enabling the production of 10-oxo-11-phytoenoic acid (10-OPEA). While studying fungal infection by Southern leaf blight (Cochliobolus heterostrophus) in maize, scientists at the Center for Medical, Agricultural and Veterinary Entomology in Gainesville, FL, discovered a novel series of 10-OPEA derived 12- and 14-carbon metabolites, collectively termed ‘death acids’ (DAs). DAs exceed jasmonate abundance in fungal infected tissues, display antibiotic activity, act as signals that induce resistance gene expression, and exhibit specificity in triggering cell death. While structurally similar to jasmonates, DAs display specialized roles in plant defense.

Technical Abstract: Plant cellular damage promotes the interaction of lipoxygenases (LOX) with free fatty acids to yield 9- and 13-hydroperoxides which are further metabolized into diverse oxylipins. The enzymatic action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, jointly known as jasmonates. As defense metabolites, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A conceptually parallel pathway involving 9-LOX activity on linoleic acid leads to the production of 10-oxo-11-phytoenoic acid (10-OPEA). Despite the structural similarity to jasmonates, physiological roles for 10-OPEA have remained unclear. In developing maize (Zea mays) leaves, fungal infection by Southern leaf blight (Cochliobolus heterostrophus) results in the localized production of 10-OPEA and a series of related 12- and 14-carbon metabolites, collectively termed ‘Death acids (DA)’. While typically absent, 10-OPEA becomes wound-inducible within fungal-infected tissues. As a direct defense, 10-OPEA suppresses the growth of mycotoxigenic fungi (Aspergillus flavus and Fusarium verticillioides) and the insect herbivore Helicoverpa zea. Both 12-OPDA and 10-OPEA equally promote the transcription of numerous defense genes encoding glutathione S-transferases, cytochrome P450s, and pathogenesis-related proteins; however, 10-OPEA is a comparatively weak elicitor of protease inhibitor transcript accumulation. Consistent with a role in dying tissue, 10-OPEA exhibits significant potency and specificity in triggering ion leakage and cell death, which is significantly inhibited by maize cystatin-9 (ZmCC9). Unlike widely encountered jasmonates, functions of 10-OPEA and associated DAs are consistent with specialized roles in local defense reactions.