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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM053940-05A2
Application #
6472590
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Shapiro, Bert I
Project Start
1996-06-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
5
Fiscal Year
2002
Total Cost
$240,686
Indirect Cost
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
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Swem, Lee R; Gong, Xing; Yu, Chang-An et al. (2006) Identification of a ubiquinone-binding site that affects autophosphorylation of the sensor kinase RegB. J Biol Chem 281:6768-75
Dragnea, Vladimira; Waegele, Matthias; Balascuta, Septimiu et al. (2005) Time-resolved spectroscopic studies of the AppA blue-light receptor BLUF domain from Rhodobacter sphaeroides. Biochemistry 44:15978-85
Anderson, Spencer; Dragnea, Vladimira; Masuda, Shinji et al. (2005) Structure of a novel photoreceptor, the BLUF domain of AppA from Rhodobacter sphaeroides. Biochemistry 44:7998-8005
Swem, Danielle L; Swem, Lee R; Setterdahl, Aaron et al. (2005) Involvement of SenC in assembly of cytochrome c oxidase in Rhodobacter capsulatus. J Bacteriol 187:8081-7
Nomata, Jiro; Swem, Lee R; Bauer, Carl E et al. (2005) Overexpression and characterization of dark-operative protochlorophyllide reductase from Rhodobacter capsulatus. Biochim Biophys Acta 1708:229-37
Smart, James L; Willett, Jonathan W; Bauer, Carl E (2004) Regulation of hem gene expression in Rhodobacter capsulatus by redox and photosystem regulators RegA, CrtJ, FnrL, and AerR. J Mol Biol 342:1171-86
Bauer, Carl; Elsen, Sylvie; Swem, Lee R et al. (2003) Redox and light regulation of gene expression in photosynthetic prokaryotes. Philos Trans R Soc Lond B Biol Sci 358:147-53; discussion 153-4
Swem, Lee R; Kraft, Brian J; Swem, Danielle L et al. (2003) Signal transduction by the global regulator RegB is mediated by a redox-active cysteine. EMBO J 22:4699-708
Kraft, Brian J; Masuda, Shinji; Kikuchi, Jun et al. (2003) Spectroscopic and mutational analysis of the blue-light photoreceptor AppA: a novel photocycle involving flavin stacking with an aromatic amino acid. Biochemistry 42:6726-34

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