It is proposed to investigate the biosynthesis of three novel microbial metabolites. These are the azoxy compound elaiomycin, which is produced by Streptomyces gelaticus, the hepatotoxic peptide cyclochloratine, which is produced by Penicillium islandicum, and the antitumor agent sparsomycin, which is found in cultures of Streptomyces sparsogenes. Earlier work has established the primary building blocks for elaiomycin and the focus of current efforts will be upon the mechanism of formation of the azoxy linkage. Cyclochloratine contains two unusual amino acid residues whose biosynthesis will be investigated: a cis 3,4-dichloroproline residue and a Beta-phenylalanine residue. The possible formation of these unusual amino acids from proline and phenylalanine will be evaluated. Sparsomycin contains a highly modified uracil moiety linked to a three carbon unit bearing a mono-oxo-dithioacetal group. Two hypotheses for the origin of the uracil moiety will be investigated and the hypothesis that the three carbon unit is derived from cysteine will be tested. The biosynthesis of the mono-oxo-dithioacetal group will also be scrutinized. The method utilized in these studies will be the administration of specifically labeled precursors to the appropriate organisms followed by location of the labels in the natural products by degradation or c.m.r. spectrometry.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA025142-07
Application #
3166704
Study Section
(SSS)
Project Start
1978-09-01
Project End
1988-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Rice University
Department
Type
Schools of Arts and Sciences
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005