142 Recent understanding of plant metabolism has made it possible to increase the iron, zinc and β-carotene (provitamin A) content in staple foods by both conventional plant breeding and genetic engineering. Improving the micronutrient composition of plant foods may become a sustainable strategy to combat deficiencies in human populations, replacing or complementing other strategies such as food fortification or nutrient supplementation. Addresses Laboratory of Human Nutrition, Institute of Food Science and Nutrition, Swiss Federal Institute of Technology, Zürich, PO Box 474, CH-8803 Rüschlikon, Switzerland *e-mail: michael.zimmermann@ilw.agrl.ethz.ch Current Opinion in Biotechnology 2002, 13:142–145 0958-1669/02/$ —see front matter © 2002 Elsevier Science Ltd. All rights reserved. Published online 6th March 2002 Abbreviations GGPP geranylgeranyl diphosphate RE retinol equivalent Introduction In developing countries, problems of politics, distribution and poverty create food shortages and undernutrition. Many populations survive largely on plant-based diets with little or no meat or dairy products. Monotonous consump- tion of cereal staples, roots or pulses, in the absence of animal tissue, can lead to deficiencies of essential vitamins and minerals. Despite improvements over the past 50 years, over 2 billion people, one-third of the world’s population, suffer from vitamin A, Zn and/or Fe deficiencies [1]. The global population, which reached 6 billion in late 1999, is estimated to climb to 8.3 billion in 2020. Most of this increase will occur in the cities of the developing world [2 • ] where the prevalence of these micronutrient deficiencies, and their associated morbidity and mortality, is highest. During the 20th century, conventional breeding produced vigorous new plant varieties and hybrids that substantially increased yields and harvest stability, and improved nutrition. But, ever-increasing populations and changing demographics in the developing countries means the struggle for food security is far from over. To meet the macronutrient and micronutrient needs of over 8 billion people by the end of the coming quarter century, it is likely that both conventional crop technology and biotechnology will be needed. Most of the research on plant breeding over the past few decades has concentrated on increasing resistance to environmental stresses, pests and pathogens [3]. Genetic engineering has even been used to improve the sensory appeal of agricultural products, such as tomatoes [4 • ]. However, the recent application of plant biotechnology to improve the nutritional content of staple food crops has perhaps the greatest potential to benefit global health [5,6,7 •• ,8 •• ]. Because poverty limits food access for much of the developing world’s population, it is important that affordable staple foods be as nutritious as possible. It may be possible to engineer synthetic pathways for many of the vitamins into plants, once the pathways are known and the corresponding genes have been cloned [9]. For example, Arabidopsis seed, like most oilseed crops, contains a high proportion of γ-tocopherol, which has only 10% of the vitamin E activity of α-tocopherol. Expression of the synthetic enzyme γ-tocopoherol methyltransferase in Arabidopsis seed resulted in the conversion of the large pool of γ-tocopherol to α-tocopherol with a corresponding 10-fold increase in vitamin E activity [10]. Improving the mineral content of plants, however, presents a different set of challenges. Unlike vitamins, which are synthesized by the plants themselves, plants must take up and store essential minerals from the soil. In this review, we focus on recent work with vitamin A and the minerals Fe and Zn. Vitamin A Half of the world’s population eat rice (Oryza sativa ) daily and depend on it as their staple food. Rice, however, is a poor source of many essential micronutrients and vitamins. In Southeast Asia, 70% of preschool children suffer from vitamin A deficiency [11]. Improved vitamin A nutrition could prevent 1 to 2 million deaths each year among children aged 1–4 years [11]. In tropical areas, rice is typically milled to remove the oil-rich aleurone layer to reduce rancidity during storage. The remaining edible portion, the endosperm, like the bran, lacks provitamin A (the plant carotenoids that are vitamin A precursors). Recently, Ye et al. [7 •• ] have used genetic engineering techniques to produce rice grains containing β-carotene, the major precursor of vitamin A. Immature rice endosperm can synthesize the intermediate compound geranylgeranyl diphosphate (GGPP). GGPP can be used to produce phytoene, an uncolored carotene, by expressing the enzyme phytoene synthase [12]. The synthesis of β-carotene from phytoene requires comple- mentation with three additional plant enzymes: phytoene desaturase and β-carotene desaturase, each catalysing the introduction of two double bonds, and lycopene β-cyclase, encoded by the lcy gene. Ye et al. [7 •• ] inserted the β-carotene biosynthetic pathway into rice endosperm via Improving iron, zinc and vitamin A nutrition through plant biotechnology Michael B Zimmermann* and Richard F Hurrell