Promiscuity of terpene synthases results in the enormous diversity of terpenes found in nature. Multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula generates 27 optically pure products from its natural substrate (2E,6E)-farnesyl diphosphate (FDP). In order to study the promiscuity of MtTPS5, (2Z,6E)-FDP, an analogue of presumptive reaction intermediates from natural reaction cascade, was utilized as a substrate. This stereoisomer induced a novel cyclization pathway leading to sesquiterpenes based on humulane, amorphene, and himachalane skeletons. Interestingly, none of these products matched those observed on incubation of MtTPS5 with natural (2E,6E)-FDP. Further determination of the absolute configuration of each product helped rebuild the stereochemical route of the reaction cascade. Interestingly, the presence of only one enantiomer of each product was observed, indicating the highly stereospecific nature of the enzymatic reaction. Substrate promiscuity of terpene synthases provides organism access to novel chemical bouquets of high optical purity by utilizing existing enzymes. The presence of this mechanism was indicated by the presence of these alternate products in natural herbivore-induced volatiles of M. truncatula.