Specialized metabolic pathways: hedonistic and medicinal applications
A. Vainstein
The Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture
Faculty of Agriculture, Food and Environment
The HebrewUniversity of Jerusalem
The industrial production of plant metabolites for food, aroma and pharmaceutical applications is an important biotechnological goal. In many instances, however, the levels of the compounds of interest are too low for commercial exploitation, even in native plants. Current production of plant secondary metabolites depends on either inefficient and rather expensive extraction methods that utilize the native plant, or chemical synthesis of these compounds, creating a product that is less preferred by consumers.
Despite the high commercial value of secondary metabolites, as well as their high intrinsic importance for the well-being of the natural host organism, details on the biochemistry underlying their production are still rather sketchy. To explore metabolic fluxes and identify genes that perform key functions in the production of phenylpropanoids and terpenoids—two major metabolic pathways—we employed various high-throughput approaches in conjunction with transgenics in both plants and yeast. Functional characterization of novel plant transcription factors allowed us to genetically engineer plants with a ca. 10-fold increase in aroma production/emission, as well as pigmentation. We also converted yeast into a factory for the production of secondary metabolites. To enable the efficient grafting of plant metabolic pathways in a non-host organism, we first generated (through genetic modification of ca. seven genes) a yeast platform for the efficient production of plant metabolites. Integration of plant genes into different intracellular compartments in the yeast platform led to the efficient production, in yeast, of numerous plant aroma compounds. The genetically modified yeast were also used to generate wine with unique aromas. Moreover, we were the first to report the successful production of active artemisinin, the most important antimalarial drug today, in the non-host plant tobacco. Artemisinin levels in Artemisia annua, the plant from which the drug is extracted,are extremely low and unable to satisfy the world's growing demand for this compound. To achieve accumulation of artemisinin in tobacco, we constructed a plant transformation megavector for expression of all of the artemisinin-pathway genes from A. annua.To boost artemisinin production in a non-host organism, we targeted the products of artemisinin-related genes to different subcellular compartments within the transgenic tobacco, i.e. cytosol, mitochondria and chloroplast. The development of plant-based approaches for cost-effective production of the antimalarial drug artemisinin is expected to increase the supply of this much awaited remedy to one of the world's most severe infectious diseases.