Steps toward redefining taste and smell

Natural products play a key role in the process of chemosensory signalling during an early stage outside the cells, when they bind to molecular sensors (receptors), either 1) after being transported via fluid media (air or water), or 2) after coming in direct tactile contact with the receptors. This first stage is only part of the path that leads to the final interpretation of the chemical signal, involving neuroanatomical and physiological aspects, but it is certainly an ancient part, already developed in very simple forms of aquatic life devoid of complex neurophysiological systems. In spite of this, the current definitions of the chemical senses (olfaction and gustation) are mainly based on the spatial range of the senses, and only take into account the molecular, neurophysiological, and anatomical sensors involved, regardless of the natural products that are the first and essential actors in chemosensory perception. Remarkably, a vast literature entirely ignores the information provided by natural product chemists about the chemical cues available to the different sensors in both aquatic and terrestrial organisms. For example, it is widely believed that aquatic animals do not encounter volatile compounds that are insoluble in water. Surprisingly, this assumption - which is patently wrong through the eyes of a chemist who has isolated many volatile and hydrophobic natural products from marine organisms - pervades the major literature on the neuroanatomy and physiology of the sensory organs of fish and crustaceans and represents one of the most serious obstacles to an effective debate on the evolutionary history of the chemical senses. Recent publications, however, have underlined that many chemosensory cues have been instead conserved during the evolutionary transition from aquatic to terrestrial life, and that aquatic animals can recognize the presence of hydrophobic olfactory cues by a "tactile" form of chemoreception.1-3 Such arguments will be discussed here to emphasize that the information provided by marine natural product chemistry, if adequately decompartmentalized, could become a powerful tool toward a more accurate historical narrative on chemoreception and could lead to a future redefinition of the chemical senses. [1] E. Mollo, A. Fontana, V. Roussis, G. Polese, P. Amodeo, M. T. Ghiselin, Front Chem, 2014, 2, 92. [2] G. Giordano, M. Carbone, M. L. Ciavatta, E. Silvano, M. Gavagnin, M. J. Garson, K. L. Cheney, I. W. Mudianta, G. F. Russo, G. Villani, L. Magliozzi, G. Polese, C. Zidorn, A. Cutignano, A. Fontana, M. T. Ghiselin, E. Mollo, Proc Natl Acad Sci USA, 2017, 114, 3451-3456. [3] E. Mollo, M. J. Garson, G. Polese, P. Amodeo, M. T. Ghiselin, Nat Prod Rep, 2017, 34, 496-513.