Production of the Cancer-Preventive Glucoraphanin in Tobacco  

作　　者：Michael Dalgaard Mikkelsen Carl Erik Olsen Barbara Ann Halkier 

机构地区：[1]University of Copenhagen, Faculty of Life Sciences, Department of Plant Biology, Plant Biochemistry Laboratory, VKR Research Centre for Pro-Active Plants, 40 Thorvaldsensvej, DK-1871 Frederiksberg C, Copenhagen, Denmark [2]University of Copenhagen, Faculty of Life Sciences, Department of Basic Sciences and Environment/Bioorganic Chemistry, 40 Thorvaldsensvej, DK-1871 Frederiksberg C, Copenhagen, Denmark

出　　处：《Molecular Plant》2010年第4期751-759,共9页分子植物（英文版）

摘　　要：Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glu- cosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conver- sion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glu- cosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conver- sion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.

关 键 词：COMPARTMENTATION secondary metabolism/natural products AGROBACTERIUM Arabidopsis TOBACCO GLUCOSINOLATES metabolic engineering. 

分 类 号：S572[农业科学—烟草工业] S78[农业科学—作物学]