Genetic Analysis of Mg-tetrapyrrole Biosynthesis

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DESCRIPTION (provided by applicant): The tetrapyrrole biosynthetic pathway is responsible for synthesizing important metabolities such as vitamin B12, hemes, bilins and chlorophylls. The "common trunk" of the pathway, from 5-aminolevulinate to protoporphyrin IX, has received much attention owing to the fact that a number of heredity diseases (porphyrias) are caused by the overproduction of heme precursors. Clinical manifestations of overproducing these intermediates range from simple skin lesions, to psychotic disorders, to death. The vitamin B12 branch of the pathway has also received recent attention genes involved in vitamin B12 synthesis characterized from Pseudomonas denitrificans and in Salmonella typhimurium. In contrast to the wealth of information on heme and vitamin B12 synthesis, information is just emerging on the synthesis of the Mg-tetrapyrrole family of chlorophylls. In this proposal, we outline plans to perform detailed biochemical and genetic analysis of the Mg-tetrapyrrole biosynthetic pathway. This analysis includes (i) biochemical characterization of enzymes from the Mg-tetrapyrrole branch of the biosynthetic pathway, (ii) biochemical and genetic characterization of a redox responding transcription factor that regulates expression of heme, Mg-tetrapyrroles and carotenoid biosynthesis genes, as well as polypeptides that comprise the light harvesting-II portion of the photosystem. A thorough understanding of the tetrapyrrole biosynthetic pathway has some far ranging practical implications, such as the design of herbicides that target enzymes in the Mg tetrapyrrole pathway, and the health implications of overproducing tetrapyrrole end-products such as vitamin B12 and heme. It should also not be overlooked that tetrapyrrole driven photosynthesis is the primary route of capturing and supplying energy to living cells and, consequently, it is the most important source of energy in our technological world.