Vol.:(0123456789) 1 3 Planta https://doi.org/10.1007/s00425-018-3051-2 REVIEW From plant physiology to pharmacology: fusicoccin leaves the leaves Lorenzo Camoni 1  · Sabina Visconti 1  · Patrizia Aducci 1  · Mauro Marra 1 Received: 27 July 2018 / Accepted: 14 November 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Main conclusion This review highlights 50 years of research on the fungal diterpene fusicoccin, during which the molecule went from a tool in plant physiology research to a pharmacological agent in treating animal diseases. Fusicoccin is a phytotoxic glycosylated diterpene produced by the fungus Phomopsis amygdali, a pathogen of almond and peach plants. Widespread interest in this molecule started when it was discovered that it is capable of causing stomate opening in all higher plants, thereby inducing wilting of leaves. Thereafter, FC became, and still is, a tool in plant physiology, due to its ability to infuence a number of fundamental processes, which are dependent on the activation of the plasma membrane H + -ATPase. Molecular studies carried out in the last 20 years clarifed details of the mechanism of proton pump stimulation, which involves the fusicoccin-mediated irreversible stabilization of the complex between the H + -ATPase and activatory 14-3-3 proteins. More recently, FC has been shown to infuence cellular processes involving 14-3-3 binding to client proteins both in plants and animals. In this review, we report the milestones achieved in more than 50 years of research in plants and highlight recent advances in animals that have allowed this diterpene to be used as a 14-3-3 targeted drug. Keywords Diterpene phytotoxin · Plasma membrane H + -ATPase, 14-3-3 proteins · Protein–protein interaction · Drug design Introduction Phytotoxins are secondary metabolites that fungi or bacteria secrete to increase their pathogenicity during infection of plants (Möbius and Hertweck 2009; Pfeilmeier et al. 2016). Attributing to these molecules an actual role in pathogenesis is a hard and time-consuming task, whereas even more dif- cult is the investigation of the molecular mechanism of their toxicity; consequently, molecular mechanisms have been clarifed in very few cases. A notable exception is fusicoc- cin (FC, Table 1), the major metabolite produced by the fungus Phomopsis amygdali (formerly known as Fusicoc- cum amygdali Del.) In fact, more than 50 years of extensive research has led to understanding of its molecular mecha- nism of action in plants, a fact that today opens new stimu- lating basic and applied research perspectives in animals, thereby strongly renewing the interest toward the surprising properties of this molecule. Discovery and early studies The history of FC started almost 60 years ago when a group of Italian plant pathologists studied the canker dis- ease induced by P. amygdali on almond and peach trees; this disease caused heavy economic losses in the south of Italy (Graniti 1962). Infected plants showed formation of cankers on branches, as a suberi fcation response of the plant to pathogen penetration, as well as the appear- ance of necrotic areas on and wilting of distal leaves, not colonized by the pathogen (Graniti 1964). This latter symptom suggested that most of the efects of the fungus could be due to some systemically transmitted metabo- lite and prompted Ballio et al. (1964) to isolate from cul- ture fltrates of the fungus its major metabolite, named Fusicoccin A, together with several related molecules. It was successively proved that FC was actually responsible for systemic symptoms, such as leaf wilting (Turner and * Lorenzo Camoni camoni@uniroma2.it 1 Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifca, 00133 Rome, Italy