Olfaction and the complex interaction between odourant ligands and their receptors

Gas chromatography (GC)-related techniques, like comprehensive two-dimensional GC (GC × GC), GC coupled to mass spectrometry (GC-MS), or to olfactometry (GC-O), have been the gold standard in analysing volatiles, for example key food odourants (KFOs), with unprecedented sensitivities. Recently, odourant receptors (ORs), which are G protein-coupled receptors (GPCRs) dedicated to the detection of volatiles in the olfactory sensory neurons (OSNs) of the olfactory epithelium (OE) in our nose, have advocated themselves as best sensors for ecologically relevant volatiles, such as the ca. 250 key food odourants out of > 10,000 volatiles known in foods. The ability of humans to perceive and discriminate between multitudes of complex smells is granted by the presence of ~ 400 protein coding OR genes in our genome, and, acknowledging the ‘one OR type per neuron’ rule, by combinatorial odour coding at the receptor level. Based on an olfactory nerve-hardwired topographical map from the periphery/OE to the first relay station in the brain, the olfactory bulb (OB), the brain will interpret stimulus/percept-characteristic neuronal activity patterns as odour quality and intensity. A prerequisite for an understanding of odourant coding, however, is the assignment of cognate OR/agonist pairs. Cell-based assays used to assign an ecologically relevant odourant space to both rather specific or narrowly tuned, as well as broadly tuned, recombinant ORs have largely improved in the last couple of years, with respect to sensitivity, throughput, and reproducibility. However, ORs’ genetic variability due to, e.g., non-synonymous single nucleotide polymorphisms (SNPs), odourants pharmacodynamically modulating each other at the receptor level, and ORs’ largely individual performance in test cell systems, still have left 80% of human ORs without assigned ligand. Here we review recent work using state-of-the-art techniques to cope with the complex interactions of odourants, their mixtures, and metabolites with their cognate receptors and specify current knowledge of cognate odourant/agonist pairs. We highlight recent development in artificial olfaction, such as the combination of GC with electronic noses, or the realization of OR-based but cell-free sensors, all of which may finally lead to new, GC × OR-based sensor technologies.