Lead


Lay summary
Vitamins are defined as organic micronutrients that must be obtained in the human diet and are essential compounds for the survival of all organisms. Plants are critical sources of these compounds. However, despite this recognition, the importance of these compounds to plants themselves has been somewhat overlooked. Thus, in most cases the physiological, biochemical and molecular mechanisms that contribute to their synthesis, transport and accumulation in plants are not known. This is especially the case for the water-soluble B vitamins. The main focus of the proposed research will be on vitamin B1 (thiamin) and vitamin B6 (pyridoxine). The essentiality of these compounds to all organisms is recognized by their well-established function as coenzymes for numerous metabolic enzymes. Vitamin B1 is necessary for the catalytic activity of enzymes of primary metabolism. Deficiency is a widespread health problem particularly in countries where rice is a major constituent of the diet, since grain polishing removes most of the thiamin in the bran. Therefore, it is of major interest to define the pathway of biosynthesis, a virtually unexplored area in plants, which may assist in the overproduction of the vitamin for beneficial purposes. On the other hand, vitamin B6 is renowned as being involved in more functions than any other single nutrient being a cofactor for a diverse array of enzymes ranging from amino acid metabolism to antibiotic biosynthesis. In plants, it is also used in many secondary metabolite pathways e.g. alkaloid biosynthesis. More recently, some novel functions have been revealed for both of these vitamins that go beyond their role as cofactors. Vitamin B6 has been shown to be an antioxidant with potency equivalent to those of vitamins C and E, and has been implicated in alleviating oxidative, UV and salt stress in plants, while vitamin B1 has been linked to systemic acquired resistance in plants, in addition to DNA damage tolerance. The involvement of vitamins B1 and B6 in stress responses was completely unprecedented and may be of economical importance in the development of stress-tolerant crops. Furthermore, as the biosynthesis pathways exist in only bacteria, fungi and plants i.e. being absent from humans, they may provide novel drug targets. Therefore, the aims of this research are to establish the pathways of biosynthesis, decipher how their production is regulated, dissect modes of transport, assess effects of over- or under- accumulation and unravel novel roles of vitamins B1 and B6 and their mechanisms. An interdisciplinary approach will be taken combining molecular cellular biology, biochemical, biophysical, and physiological methods. The studies will predominantly be carried out in the plant model, Arabidopsis thaliana, but bacterial models will be utilized to decipher data rapidly. While these issues are of fundamental importance and are of broad interest to the scientific community, the answers to these questions may permit either the production of these compounds for beneficial effects or their depletion in the context of herbicide or antibiotic development.