Cephalosporin hydroxylase

All the enzymes contain ferrous iron. Ferrous ions are essential for the catalytic activity of butyrobetaine hydroxylase (259), proline-4- 254) and 3- 242, 243), hydroxylases, thymidine hydroxylase 260), lysine hydroxylase 261), trimethyllysine hydroxylase 247), thymine oxygenase 262—264), cephalosporin hydroxylase 249), and hydroxy-phenylpyruvate 265—267). In addition, the enzymes show a non-stoichio-metric requirement for ascorbic acid which is supposed to maintain the ion co-factor in the ferrous oxidation state (2, 242, 243, 254). Labelling studies with butyrobetaine hydroxylase 268), proline-4-hydroxylase 269), thymine oxygenase (270), cephalosporin hydroxylase (257) and hydroxy-phenylpyruvate hydroxylase (277) all indicate a common pattern of oxygen incorporation. One atom of oxygen becomes the new hydroxyl group while the other is located in one of the carboxylic acid groups of succinic acid. 

T ymidine-2 -hy droxylase Trimethyllysine 3-hydroxylase Cephalosporin hydroxylase... 

SE Jensen, DWS Westlake, S Wolfe. Deacetoxy cephalosporin C synthetase and deacetoxycephalosporin C hydroxylase are two separate enzymes in Streptomyces clavuligerus. J Antibiot 38 263-265, 1985. 

SM Samson, JE Dotzlaf, ML Slisz, GW Becker, RM Van Frank, LE Veal, WK Yeh, JR Miller, SW Queener, TD Ingolia. Cloning and expression of the fungal expandase/hydroxylase gene involved in cephalosporin biosynthesis. Bio/Technol-ogy 5 1207-1214, 1987. 

Figure 1 Biosynthetic pathway to DAC. In Cephalosporium acremonium, DAC is ace-tylated by DAC acetyltransferase to cephalosporin C. In Streptomyces clavuligerus, it is carbamoylated by L -carbamoyltransferase followed by methoxylation by C-7 hydroxylase and methyltransferase.

Jensen SE. Westlake DWS, Wolfe S. DeaceroxycephalospiHin C syniherase and ikaceroxy cephalosporin C hydroxylase are two separate enzymes in Strepiomyces cloudigenu. J Antibiot 1985 38 263-265. 

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