160200-91-9Relevant articles and documents
δ-Amino group hydroxylation of l-ornithine during coelichelin biosynthesis
Pohlmann, Verena,Marahiel, Mohamed A.
, p. 1843 - 1848 (2008)
The nonribosomally produced hydroxamate siderophore coelichelin from Streptomyces coelicolor contains the nonproteinogenic amino acids N 5-hydroxyornithine and N5-hydroxyformylornithine that are important for iron assembly. The hydroxylation of the δ-amino group of l-ornithine is catalyzed by the flavin-dependent monooxygenase CchB. During the redox reaction nicotinamide adenine dinucleotide phosphate (NADPH) and molecular oxygen are consumed and flavin adenine dinucleotide (FAD) is needed as a cofactor. During this work the monooxygenase was biochemically characterized and it could be shown that the hydroxylation of l-ornithine is most likely the first step in the biosynthesis of the siderophore coelichelin. The Royal Society of Chemistry.
Acylation of protein lysines by trichloroethylene oxide
Cai, Hongliang,Guengerich, F. Peter
, p. 327 - 335 (2007/10/03)
Stable lysine adducts were formed in proteins following reaction with trichloroethylene (TCE) oxide, the major reactive compound generated by the metabolism of TCE. The order of formation of these adducts is N6- formyllysine > N6-(dichloroacetyl)lysine >> N6-glyoxyllysine, with the ratio being influenced by the particular protein. Protein lysine adducts were also analyzed following the enzymatic oxidation of TCE with several different cytochrome P450 (P450) enzyme systems. The ratio of formyl/dichloroacetyl lysine adducts was influenced by the enzyme system that was used. Chloral and TCE oxide formation was more extensive with rat liver microsomes isolated from phenobarbital-treated rats than with rat microsomes in which P450 2E1 was induced by treatment with isoniazid or in human P450 2E1 systems. Glutathione (GSH) and GSH transferase had inhibitory effects on the reaction of TCE oxide with albumin, with formylation being attenuated much more than the formation of dichloroacetyllysine. GSH is likely to react with the reactive acyl chloride intermediates formed from TCE oxide hydrolysis, instead of direct reaction with TCE oxide, as judged by the lack of an effect of GSH on the rate of decomposition of TCE oxide. Studies with the model enzymes aldolase and glucose-6-phosphate dehydrogenase, both known to have sensitive lysine groups, indicate that TCE oxide has effects similar to known acylating agents that form the same adducts; concentrations of TCE oxide (or the model acylating agents) in the low-millimolar range were needed for inhibition. The characterization of TCE-derived protein adducts can be used as a basis for consideration of the exposure and risk of TCE to humans. Human P450 2E1 was less likely to oxidize TCE to form TCE oxide and protein lysine adducts than rat P450 2B1, and the difference is rationalized in terms of the influence of the protein on chloride migration in an enzyme reaction intermediate.
