The purpose of the proposed research is to elucidate tho biochemistry, physiology, and structure of new coenzymes and vitamins that have been discovered in methanogenic bacteria. In the history of biochemistry, microbes have played a pivotal role in the assay of vitamins as well as in the elucidation of the biochemical function of vitamins and coenzymes. To completely understand cell chemistry is important, for biochemical deficiences produce a diseased state. So far the structures of 6 new coenzymes of methanogens have been documented. It is our goal to define the biochemistry of carbon dioxide reduction to methane, a process which requires the participation of these coenzyme. The major specific aims for this applications are; (i) to study the activation and reduction of carbon dioxide that leads to the formation of a formyl group on the coenzyme, methanofuran, a new method of carbon dioxide fixation; (ii) to study the reduction of a methylene group attached to the coenzyme, tetrahydromethanopterin, and define the products of the reaction; (iii) to define the electron carriers that are involved in these enzymatic reductive reactions; (iv) to study the reductive regeneration of the mercapto form of each of two coenzymes (HS-CoM and 7- mercaptoheptanoylthreonine phosphate) from their heterodisulfide, which is the oxidized product of the terminal methanogenic reaction; (v) to isolate and determine the structure of a vitamin required for the growth of Methanomicrobium mobile. We cannot predict whether these coenzymes will be of chemotherapeutic value in human disease, or whether they will contribute only in a general understanding of biochemistry. The discovery of the archaebacteria is only about a decade old, and since these organisms differ in many ways from typical bacterial, it is important to fully document their biochemistry and identify potential uses to benefit man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012277-20
Application #
3125154
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1974-09-01
Project End
1994-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
20
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Kuhner, C H; Lindenbach, B D; Wolfe, R S (1993) Component A2 of methylcoenzyme M reductase system from Methanobacterium thermoautotrophicum delta H: nucleotide sequence and functional expression by Escherichia coli. J Bacteriol 175:3195-203
Woo, G J; Wasserfallen, A; Wolfe, R S (1993) Methyl viologen hydrogenase II, a new member of the hydrogenase family from Methanobacterium thermoautotrophicum delta H. J Bacteriol 175:5970-7
Olson, K D; Chmurkowska-Cichowlas, L; McMahon, C W et al. (1992) Structural modifications and kinetic studies of the substrates involved in the final step of methane formation in Methanobacterium thermoautotrophicum. J Bacteriol 174:1007-12
Reddy, D M; Crain, P F; Edmonds, C G et al. (1992) Structure determination of two new amino acid-containing derivatives of adenosine from tRNA of thermophilic bacteria and archaea. Nucleic Acids Res 20:5607-15
Kuhner, C H; Smith, S S; Noll, K M et al. (1991) 7-Mercaptoheptanoylthreonine phosphate substitutes for heat-stable factor (mobile factor) for growth of Methanomicrobium mobile. Appl Environ Microbiol 57:2891-5
Olson, K D; McMahon, C W; Wolfe, R S (1991) Light sensitivity of methanogenic archaebacteria. Appl Environ Microbiol 57:2683-6
Olson, K D; McMahon, C W; Wolfe, R S (1991) Photoactivation of the 2-(methylthio)ethanesulfonic acid reductase from Methanobacterium. Proc Natl Acad Sci U S A 88:4099-103
Bobik, T A; DiMarco, A A; Wolfe, R S (1990) Formyl-methanofuran synthesis in Methanobacterium thermoautotrophicum. FEMS Microbiol Rev 7:323-6
Jablonski, P E; DiMarco, A A; Bobik, T A et al. (1990) Protein content and enzyme activities in methanol- and acetate-grown Methanosarcina thermophila. J Bacteriol 172:1271-5
DiMarco, A A; Sment, K A; Konisky, J et al. (1990) The formylmethanofuran:tetrahydromethanopterin formyltransferase from Methanobacterium thermoautotrophicum delta H. Nucleotide sequence and functional expression of the cloned gene. J Biol Chem 265:472-6

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