A Rhizosphere Fungus Enhances Arabidopsis Thermotolerance through Production of an HSP90 Inhibitor

Abstract

The molecular chaperone HEAT SHOCK PROTEIN90 (HSP90) is essential for the maturation of key regulatory proteins in eukaryotes and for the response to temperature stress. Earlier, we have reported that fungi living in association with plants of the Sonoran desert produce small molecule inhibitors of mammalian HSP90. Here, we address whether elaboration of the HSP90 inhibitor monocillin I (MON) by the rhizosphere fungus Paraphaeosphaeria quadriseptata affects plant HSP90 and plant environmental responsiveness. We demonstrate that MON binds Arabidopsis (Arabidopsis thaliana) HSP90 and can inhibit the function of HSP90 in lysates of wheat (Triticum aestivum) germ. MON treatment of Arabidopsis seedlings induced HSP101 and HSP70, conserved components of the stress response. Application of MON, or growth in the presence of MON, allowed Arabidopsis wild type but not AtHSP101 knockout mutant seedlings to survive otherwise lethal temperature stress. Finally, cocultivation of P. quadriseptata with Arabidopsis enhanced plant heat stress tolerance. These data demonstrate that HSP90-inhibitory compounds produced by fungi can influence plant growth and responses to the environment.

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases

“…In contrast, radilarin displayed a more potent heat shock response modulatory activity than dehydrocurvularin, although both compounds were significantly less active than monocillin I, used as the positive control (Table 1). Although the RAL 14 monocillin I and its congeners (radicicol and the pochonins) inhibit Hsp90 (10,37), the mechanism of heat shock modulation by the DAL 12 7 has not been clarified (36). The two additional DAL 14 compounds isolated here, 14,15-dihydroradilarin (16) and lasilarin (17), showed no cytotoxicity or heat shock induction activity at 5 μM, stressing the importance of the 14(E) double bond for both activities.…”

Symbiosis as a source of selectable epigenetic variation: taking the heat for the big guy

“…Growing the HSP-101 mutant P. quadriseptata in a heat stress environment had no effect on thermotolerance, supporting the theory that P. quadriseptata is conferring thermotolerance by affecting the levels of HSP-101. The implications of this may be wide-ranging (McLellan et al 2007). P. quadriseptata is not only found in cactuses, but also in maize (Zea mays), a species that is not phylogenetically close to O. leptocaulis.…”

“…In order to demonstrate that monocillin I (MON) can enhance thermotolerance in Arabidopsis thaliana (a model system plant that does not normally express MON), McLellan et al (2007) first confirmed that MON had cross-species affinity to Arabidopsis HSP-90. Once MON was shown to have affinity to A. thaliana HSP-90, P. quadriseptata was incubated within A. thaliana and heat shocked.…”

“…P. quadriseptata is not only found in cactuses, but also in maize (Zea mays), a species that is not phylogenetically close to O. leptocaulis. It may be that fungal production of HSP-90 inhibitors is a common means of thermotolerance in desert and other plants that are consistently exposed to heat stress (McLellan et al 2007).…”

Rational reprogramming of fungal polyketide first-ring cyclization

“…Curvularins modulate the mammalian immune system by repressing the inducible nitric oxide synthase (21,22). In addition, both monocillin II (1) and 10,11-dehydrocurvularin (2) act as promising broad spectrum inhibitors of various cancer cell lines in vitro by overwhelming the heat shock response, an evolutionarily conserved coping mechanism of eukaryotic cells that maintains protein homeostasis (23)(24)(25)(26).…”