Secretion of Secondary Metabolites by ATP-Binding Cassette Transporters in Plant Cell Suspension Cultures

The substrate specificity of the yeast (Saccharomyces cerevisiae) pleiotropic drug resistance (PDR)-type ATP-binding cassette (ABC) transporters is extended to plant secondary metabolites of the tropane alkaloid family. Functional analysis of yeast PDR5 genes in transgenic tobacco (Nicotiana tabacum L. cv Bright-Yellow 2 [BY-2]) cell lines suggest that PDR genes can be used to stimulate the secretion of secondary metabolites in plant cell suspension cultures. Higher plants are capable of producing an enormous number of low-molecular weight compounds, often with distinct and very complex structures (Verpoorte, 2000). In addition to their importance for the plant itself, numerous secondary metabolites are also of high value to humans because of their interesting biological activities. Many of these compounds are difficult to produce because they accumulate at extremely low levels in often rare and exotic plant species. The problems related with obtaining useful metabolites from natural resources might potentially be circumvented using cell cultures. Nevertheless, the enormous biosynthetic potential of plant cells is still unexploited, in sharp contrast with that of microorganisms (Hutchinson, 1994; Verpoorte and Memelink, 2002). Increasing the metabolic flux through a biosynthetic pathway to improve the production of certain compounds in plant cells has been the prime target for metabolic engineering in the past. However, low productivity may also be the result of the intrinsic toxicity of plant secondary metabolites, including for the producing plant cell itself. Furthermore, catabolism or intracellular accumulation of plant secondary metabolites may interfere with their production and hamper subsequent purification.