Tomato breeding has been tremendously efficient in increasing fruit quality and quantity but did not focus on improving herbivore resistance. The biosynthetic pathway for the production of 7-epizingiberene in a wild tomato was introduced into a cultivated greenhouse variety with the aim to obtain herbivore resistance. 7-Epizingiberene is a specific sesquiterpene with toxic and repellent properties that is produced and stored in glandular trichomes. We identified 7-epizingiberene synthase (ShZIS) that belongs to a new class of sesquiterpene synthases, exclusively using Z-Z-farnesyl-diphosphate (zFPP) in plastids, probably arisen through neo-functionalization of a common ancestor. Expression of the ShZIS and zFPP synthases in the glandular trichomes of cultivated tomato resulted in the production of 7-epizingiberene. These tomatoes gained resistance to several herbivores that are pests of tomato. Hence, introduction of this sesquiterpene biosynthetic pathway into cultivated tomatoes resulted in improved herbivore resistance.metabolic engineering | terpenoid | white fly | spider mite | promoter H erbivorous insects pose serious problems in agricultural production areas. On commercial tomato, whiteflies, spider mites, and aphids are major pests, not only by the feeding damage they cause, but also because they transmit devastating viruses that can cause losses up to 100% (1). Production of tomato, a crop with considerable economic importance, reached 145,751,507 tons worldwide in 2010, representing a value of 53.3 billion dollars (www.fao.org). In general, wild tomatoes are far less attractive to pests than cultivated tomatoes due to an elevated or qualitatively different production of an array of defense compounds such as alkaloids, phenolic compounds, and terpenes.Toxic and repellent compounds are mostly produced in glandular trichomes, autonomous epidermal protrusions specialized in efficient production, storage, and release of defense compounds (2). These glands have long been regarded as economically important and challenging targets for bioengineering (2). Confining metabolic changes to trichomes ensures that the plant metabolism and crop yield remains unaffected.Terpenes constitute the largest and most diverse class of plantproduced secondary compounds that maintain a variety of biological functions and applications, including anticancer (taxol) and antimalarial (artemisin) drugs, in flavor and fragrance industry, and for crop improvement through enhanced pest resistance. Wild tomato sesquiterpenes and derivatives have been implicated in defense against herbivores (3-5). Sesquiterpenes are C 15 -terpenes predominantly derived from precursors of the cytosolic mevalonate pathway where the C 5 -isoprene units isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) are assembled into C 15 E-E-farnesyl diphosphate (FPP) by FPP synthase (FPS) and converted by specific sesquiterpene synthases. However, it was recently shown that some wild tomato species contain a sesquiterpene pathway that is confined to ...