The emerging field of transport engineering of plant specialized metabolites Hussam Hassan Nour-Eldin and Barbara Ann Halkier From a biotechnological perspective transport processes represent attractive targets for modulation of metabolite levels and are the foundation for the emerging field of transport engineering. Potential applications of transport engineering include control of metabolite accumulation in a tissue-specific manner in crop plants as well as increased yields of commercially valuable compounds produced in synthetic biology approaches. Within specialized metabolism, recent advances include identification of not only vacuolar but now also plasma membrane-localized transporters and neo- functionalization of members of primary metabolite transporter families to include specific roles in transport of specialized metabolites. As glucosinolates are specialized metabolites of the model plant Arabidopsis, glucosinolate transport processes emerge as a model system for studying transport of specialized metabolites. Address DynaMo Centre of Excellence, Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark Corresponding author: Halkier, Barbara Ann (bah@life.ku.dk) Current Opinion in Biotechnology 2013, 24:263–270 This review comes from a themed issue on Plant biotechnology Edited by Natalia Dudareva and Dean DellaPenna For a complete overview see the Issue and the Editorial Available online 4th October 2012 0958-1669/$ – see front matter, # 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.copbio.2012.09.006 Introduction Plants synthesize a vast number of specialized metabolites, which enable these sessile organisms to interact and adapt to the ever-changing environment. Some of the com- pounds are high-value nutraceuticals and pharmaceuticals, which has primed a desire to establish production platforms through engineering of the requisite biosynthetic pathways in various host organisms. In agriculture, toxic defense compounds in edible parts of crops (e.g. seeds or tubers) reduce their nutritional value [1,2]. Previous approaches to reduce the amounts of toxic defense compounds have focused on abolition of biosynthetic pathways [3–7]. Often, however, these approaches negatively affect plant fitness owing to impact on processes such as susceptibility to biotic or abiotic stresses [1,8,9]. Specialized metabolites are often stored in specific tissues, cell types or subcellular compart- ments, which are spatially distinct from the sites of bio- synthesis [10]. This necessitates intracellular and intercellular transport of both pathway intermediates and end products. From a biotechnological perspective, targeting of transport processes potentially offers the means to control the accumulation of specialized metab- olites in a tissue-specific manner without compromising biosynthetic and hence defense capability in non-target tissues. Such approaches have created the foundation for the emerging field coined transport engineering. Plant transport highways Long distance transport of metabolites between source and sink tissues of plants is facilitated by transport path- ways in two tissues: the xylem and the phloem. These consist of, respectively, dead xylem vessels facilitating upward movement of water and compounds from roots, and the sieve elements facilitating phloem movement from source to sink tissues. The source–sink transport route utilized predicts which membrane barriers metab- olites must cross in order to access the long distance transport pathways and consequently the number and kind of transport proteins involved. Membrane barriers do not restrict the interface between the apoplast (extra- cellular space) and the xylem vessels, and therefore metabolites need only to be exported from cells into the apoplast adjacent to the xylem to access this transport pathway. In comparison, sieve elements and the associ- ated companion cells are separated from the apoplast by a plasma membrane and entry into the phloem pathway typically requires the additional activity of a plasma membrane-localized importer (Figure 1). One may anticipate that transporters at the different barriers are not equally suitable for transport engineering approaches. However, transporters that reduce export out of source cells into the apoplast, or transporters at the entry point to the transport highway (in the case of phloem transport) are likely targets for engineering of long distance trans- port (Figure 1). Entry or exit from subcellular storage vacuoles in either source or sink tissues may constitute additional targets. Model systems for studying long distance transport of specialized metabolites Alkaloid model transport system Thus far, nicotine, the alkaloid characteristic to Nicotiana species, has constituted a major model system for study- ing long distance transport of specialized metabolites from roots to leaves via the xylem, and 4 transporters Available online at www.sciencedirect.com www.sciencedirect.com Current Opinion in Biotechnology 2013, 24:263–270