Abstract

Mechanism of biosynthesis of long chain alkanes, alkane diols, 3- hydroxy acids, methyl-branched acids, erythronolide, and wax esters will be elucidated by purification and characterization of the relevant enzymes from meibomian glands, harderian glands, uropygial glands, Mycobacterium tuberculosis bovis, Streptomyces erythreus, Euglena gracilis and Pisum sativum. The structural relationship between fatty acid synthase and chain-elongating mycocerosic acid synthase will be established by cloning and sequencing their genes from M. bovis. The mechanism of interaction between fatty acid synthase and S-acyl fatty acid synthase thioesterase will be elucidated by chemical modification and fluorescence energy transfer. Structures of cDNA and the genes for S-acyl fatty acid synthase thioesterase, the thioesterase domain of fatty acid synthase and thioesterase B from mallard ducks will be determined to elucidate the structural and functional relationships among thioesterases. The role of peroxisomes in the production of sebaceous gland lipids will be elucidated. The mechanism of hormonal induction of peroxisome proliferatopm om the sebacceous glands will be elucidated one or two peroxisomal enzymes that are highly induced in the duck uropygial glands will be purified and their cDNA and genes will be cloned. The mechanism of hormonal stimulation of these genes and suppression of the thioesterase gene by estrogen will be studied. Structure of malonyl-CoA decarboxylase from Streptomyces erythreus and goose uropygial gland will be determined by nucleotide sequencing of cloned DNA. The structure and mechanism of tissue specific expression of malonyl- CoA decarboxylase gene will be elucidated and the mechanisms by which this normally mitochondrial enzyme is made to accumulate int he cytoplasm of the goose uropygial gland will be elucidated. The mechanism and regulation of biosynthesis of the above natural products are known to be relevant to a variety of health problems from acne to cancer and the proposed research is expected to fill major gaps in our knowledge of this area.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM018278-21
Application #
3269232
Study Section
Biochemistry Study Section (BIO)
Project Start
1987-07-01
Project End
1991-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
21
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Engineering
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Rose, T M; Schultz, E R; Sasaki, G C et al. (1994) Nucleotide sequence and genomic structure of duck acyl-CoA binding protein/diazepam-binding inhibitor: co-localization with S-acyl fatty acid synthase thioesterase. DNA Cell Biol 13:669-78
Hsieh, Y J; Kolattukudy, P E (1994) Inhibition of erythromycin synthesis by disruption of malonyl-coenzyme A decarboxylase gene eryM in Saccharopolyspora erythraea. J Bacteriol 176:714-24
Hwang, C S; Kolattukudy, P E (1993) Molecular cloning and sequencing of thioesterase B cDNA and stimulation of expression of the thioesterase B gene associated with hormonal induction of peroxisome proliferation. J Biol Chem 268:14278-84
Mathur, M; Kolattukudy, P E (1992) Molecular cloning and sequencing of the gene for mycocerosic acid synthase, a novel fatty acid elongating multifunctional enzyme, from Mycobacterium tuberculosis var. bovis Bacillus Calmette-Guerin. J Biol Chem 267:19388-95
Hiremath, L S; Kessler, P M; Sasaki, G C et al. (1992) Estrogen induction of alcohol dehydrogenase in the uropygial gland of mallard ducks. Eur J Biochem 203:449-57
Courchesne-Smith, C; Jang, S H; Shi, Q et al. (1992) Cytoplasmic accumulation of a normally mitochondrial malonyl-CoA decarboxylase by the use of an alternate transcription start site. Arch Biochem Biophys 298:576-86
Dennis, M; Kolattukudy, P E (1992) A cobalt-porphyrin enzyme converts a fatty aldehyde to a hydrocarbon and CO. Proc Natl Acad Sci U S A 89:5306-10
Kikuchi, S; Rainwater, D L; Kolattukudy, P E (1992) Purification and characterization of an unusually large fatty acid synthase from Mycobacterium tuberculosis var. bovis BCG. Arch Biochem Biophys 295:318-26
Dennis, M W; Kolattukudy, P E (1991) Alkane biosynthesis by decarbonylation of aldehyde catalyzed by a microsomal preparation from Botryococcus braunii. Arch Biochem Biophys 287:268-75
Kolattukudy, P E; Bohnet, S; Sasaki, G et al. (1991) Developmental changes in the expression of S-acyl fatty acid synthase thioesterase gene and lipid composition in the uropygial gland of mallard ducks (Anas platyrhynchos). Arch Biochem Biophys 284:201-6

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