O-Acetyltransferases

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

Salutaridinol 7-0-acetyltransferase catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-Oacetate, the immediate precursor of thebaine along the morphine biosynthetic pathway in P. somniferum (Fig. 10.7).26 Acetyl CoA-dependent acetyltransferases have an important role in plant alkaloid metabolism. They are involved in the synthesis of monoterpenoid indole alkaloids in medicinal plant species such as Rauwolfia serpentina. In this plant, the enzyme vinorine synthase transfers an acetyl group from acetyl CoA to 16-epi-vellosimine to form vinorine. This acetyl transfer is accompanied by a concomitant skeletal rearrangement from the sarpagan- to the ajmalan-type (reviewed in2). An acetyl CoA-dependent acetyltransferase also participates in vindoline biosynthesis in Catharanthus roseus, the source of the chemotherapeutic dimeric indole alkaloid vinblastine (reviewed in2). Acetyl CoA deacetylvindoline 4-O-acetyltransferase catalyzes the last step in vindoline biosynthesis. A cDNA encoding acetyl CoA deacetylvindoline 4-0-acetyltransferase was recently successfully isolated.27... 

Salutaridinol 7-O-acetyltransferase was purified to apparent electrophoretic homogeneity from P. somniferum cell suspension cultures and the amino acid sequence of ten endoproteinase Lys-C-generated peptides was determined.28 A comparison of these amino acid sequences with those available in the GenBank/EMBL sequence databases indicated no relevant similarity to known proteins. The first attempt to isolate a cDNA encoding salutaridinol 1-0-... 

The translation of the sequence of the cDNA encoding deacetylvindoline 4-O-acetyltransferase compared to other putative plant acetyltransferases revealed a conserved region near the carboxy terminus of the proteins. This sequence was used to design a degenerate antisense oligodeoxynucleotide primer for PCR. The sense primer was based upon an internal peptide sequence of salutaridinol 7-0-acetyltransferase. This approach finally yielded a partial cDNA that encoded salutaridinol 7-O-acetyltransferase. The full-length clone was obtained by RACE-PCR and was functionally expressed in S. frugiperda Sf9 cells.28 The amino acid sequence of salutaridinol 7-O-acetyltransferase is most similar (37% identity) to that of deacetylvindoline acetyltransferase of C. roseus.27... 

RNA gel blot analysis of several members of the genus Papaver demonstrated that salutaridinol 7-O-acetyltransferase transcript accumulated in three-week-old seedlings of P. orientale and P. bracteatum, though not in P. atlanticum or P. nudicaule % P. orientale accumulates the alternate biosynthetic precursor oripavine, and P. bracteatum accumulates the morphine biosynthetic precursor... 

Fig. 10.8 Selected cDNAs isolated in recent years that encode enzymes involved in the biosynthesis of various classes of isoquinoline alkaloids. 6-OMT, norcoclaurine 6-0-methyltransferase 23 CYP80A1, berbamunine synthase 19 CYP80B1, (S)-A-methylcoclaurine 3 -hydroxylase 20 CPR, cytochrome P-450 reductase 29 4 -OMT, (5)-3 -hydroxy-A-methylcoclaurine 4 -0-methyltransferase 30 BBE, berberine bridge enzyme 12 SalAT, salutaridinol 7-O-acetyltransferase 28 COR, codeinone reductase.25...

LENZ, R., ZENK, M.H., Acetyl coenzyme A salutaridinol 7-O-acetyltransferase from Papaver somniferum plant cell cultures, J. Biol. Chem., 1995, 270, 31091-31096. 

ST-PIERRE, B., LAFLAMME, P ALARCO, A.-M., DE LUCA, V., The terminal O-acetyltransferase involved in vindoline biosynthesis defines a new class of proteins responsible for coenzyme A-dependent acyl transfer, Plant J., 1998,14, 703-713. 

GROTHE, T., LENZ, R KUTCHAN, T.M., Molecular characterization of the salutaridinol 7-O-acetyltransferase involved in morphine biosynthesis in opium poppy Papaver somniferum, J. Biol. Chem. 2001,276, 30717-30723. 

CARNITINE O-ACETYLTRANSFERASE CARNITINE O-OCTANOYLTRANSFERASE CARNITINE O-PALMITOYLTRANSFERASE CARNOSINASE CARNOSINE SYNTHETASE CARNOT CYCLE... 

GLYCINE ACETYLTRANSFERASE HOMOCITRATE SYNTHASE HOMOSERINE O-ACETYLTRANSFERASE... 

HOMOPHILIG INTERAGTION HOMOSERINE O-ACETYLTRANSFERASE Homoserine dehydratase,... 

Einisto, P., M. Watanabe, M. Ishidate, and T. Nohmi, Mutagenicity of 30 Chemicals in Salmonella typhimurium Strains Possessing Different Nitroreductase or O-Acetyltransferase Activities, Mutat. Res., 259, 95-102 (1991). 

O-acetyltransferase has preliminarily been called218,230 acetyl-CoAuV-acylneuraminate-9(7)-0-acetyltransferase (EC 2.3.1.45). 

N-Acylneuraminate-9(7)-0-acetyltransferase seems to be widespread in Nature, as sialic acids O-acetylated in the side chain are found in many animal species, including man (see Section II). However, enzyme activity has thus far been measured only in bovine, submandibular gland and in bovine serum. The 4-O-acetyltransferase appears... 

The final step in the biosynthesis of CPC (Fig. 1) is catalyzed by acetyl CoA deacetylcephalosporin C O-acetyltransferase (DAC-AT). Fujisawa et al. [48] showed that cell-free extracts of a CPC-producing strain readily converted DAC and acetyl-1-[14C]-CoA to labeled CPC. They utilized this novel assay system to characterize several mutants that accumulated DAC and correctly proposed that... 

A Matsuda, H Sugiura, K Matsuyama, H Matsumoto, S Ichikawa, KI Komatsu. Cloning and disruption of the cefG gene encoding acetyl coenzyme A deacetylcephalosporin C O-acetyltransferase from Acremonium chrysogenum. Biochem Biophys Res Commun 186 40-46, 1992. 

S Gutierrez, J Velasco, FJ Fernandez, JF Martin. The cefG gene of Cephalosporium acremonium is linked to the ce/EF gene and encodes a deacetylcephalosporin C acetyltransferase closely related to homoserine O-acetyltransferase. J Bacteriol 174 3056-3064, 1992. 

DE LUCA, V., BALSEVICH, J., KURZ, W.G.W., Acetylcoenzyme A deacetylvindoline O-acetyltransferase, a novel enzyme from Catharanthus. J. Plant Physiol., 1985,121,417-428. 

Fig. 8.1 Sequence of reactions and pathways involved in the biosynthesis of indole alkaloids in Catharanthus roseus. The dotted lines indicate multiple and/or uncharacterized enzyme steps. Tryptophan decarboxylase (TDC), Geraniol Hydroxylase (GH), Deoxyloganin synthase (DS), Secologanin Synthase (SLS) Strictosidine synthase (STR1), Strictosidine glucosidase (SG), Tabersonine-16-hydroxylase (T16H), Tabersonine 6,7-eposidase (T6,7E), Desacetoxyvindoline-4-hydroxylase (D4H), Deacetyl-vindoline-4-O-acetyltransferase (DAT) and Minovincinine-19-O-acetyltransferase (MAT) represent some of the enzyme steps that have been characterized.

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