Hydroxylamines biosynthesis

A question occurs as to why the bacterial enzyme has such a complicated structure, because hydroxylamine is oxidized to nitrite by the catalysis of ferric ion under aerobic conditions. In the nonenzymatic reaction, molecular oxygen is incorporated into nitrite formed by the oxidation of hydroxylamine, while the oxygen atom of water is incorporated into nitrite formed by the enzymatic oxidation of hydroxylamine (see below) (Yamanaka and Sakano, 1980 Andersson and Hooper, 1983). The mechanism in the bacterial oxidation of hydroxylamine will have been devised to reserve efficiently the energy of the reaction for the biosynthesis of adenosine triphosphate (ATP). 

Two of the four electrons generated from hydroxylamine oxidation are used to support the oxidation of additional ammonia molecules, while the other two electrons enter the electron transfer chain and are used for CO2 reduction and ATP biosynthesis [153,154]. 

Yamazaki et al. (221) have postulated that the tryptoquivalines may be biogenetically derived from four amino acids tryptophan, anthranilic acid, valine and alanine. Deoxynortryptoquivalone is thought to be the first compound formed in the biosynthesis of the tryptoquivaline series. Oxidation of the secondary amine in this compound to a hydroxylamine would result in nortryptoquivalone. Oxidative loss of the side-chain would lead to FTE or FTJ. Alternatively, reduction of the side-chain carbonyl group would afford nortryptoquivaline. The geminal dimethyl group at C-15 may result from incorporation of a Cj-unit into deoxynortryptoquivalone or from the direct participation of methylalanine rather than alanine in the initial step of the biosynthesis. 

The biogenesis of the N-hydroxyamide bond is an interesting problem 115). That it may involve oxidation of the a- or co-amine group of an amino acid to a hydroxylamine derivative (Scheme 14, path a) was observed in the biosynthesis of ferrichrome (5) 116), hadacidin (13) (25, 117) and aerobactin (8) 118). 

The B2 protein contains 2 moles of non-heme iron per molecule of enzyme. The iron is bound tightly, but can be removed by dialysis against 8-hydroxyquinoline. The iron-depleted enzyme is inactive, but activity may be restored by addition of iron. The B2 protein has a characteristic absorption peak at 410 m/i, which is attributed to its iron content. Hydroxyurea, which is known to inhibit DNA biosynthesis, evidently achieves this effect through interaction with the B2 protein (7). When the B2 protein is treated with hydroxyurea, the characteristic absorption at 410 m/t disappears, and the resulting loss of enzyme activity parallels the decrease in absorbance at that wavelength. Similar effects are obtained with hydroxylamine or hydrazine. 

The biosynthesis of glutamine from glutamic acid and NH3 by enzyme preparations from liver and brain has been shown to require ATP and magenesium (1, 2). It has been found further that hydroxylamine can be substituted for NHs, resulting in the formation of glutamohydroxamic... 

To more directly assess the role of octanal and 1-octanol in /2-heptane biosynthesis, xylem sections were incubated with 1-octanol and [ " CJoctanal. Incubation of xylem sections with 10 dpm octanal resulted in the incorporation of into /2-heptane, although the majority of radiolabel was recovered as 1-octanol. Incubation of xylem sections with 10 dpm 1-octanol also resulted in incorporation of radiolabel into /2-heptane, and a small amount of radiolabel was incorporated into octanal. To determine whether 1-octanol is first oxidized to the aldehyde before conversion to n-heptane, xylem sections were co-incubated with 10 dpm 1-octanol and 500 mM hydroxylamine. No radiolabel was incorporated into /2-heptane, but was incorporated into octyl oximes. 

In the biosynthesis of glutamine from glutamate and ammonia it is the y-carboxyl of glutamic acid which is activated, and the cleavage of ATP to provide the 2500-4000 calories for formation of the amide bond takes place so that ADP and P are formed rather than AMP and PP. Glutamic add can also form amide bonds with hydroxylamine, hydrazine or methylamine. 

The majority of jS-lactam syntheses are dependent on the formation of the N—C bond, a process that mimics the proposed biosynthesis. However, strong bases are usually required to effect the ring closure and this leads to side-reactions. Now a method for the formation of iV-hydroxy-jS-lactams has been devised using O-substituted hydroxylamines and suitable carboxylic acids as shown in Scheme 127. 

The two antibiotics with which PPIs synergize are amoxicillin and clarithromycin. The former antibiotic inhibits cell wall biosynthesis by inhibiting peptidyl transferase and by binding to other proteins in the cell wall biosynthesis pathways. Cell division is therefore required for the bactericidal action of this class of antibiotic. Clarithromycin binds to the 23S RNA and thereby inhibits protein synthesis. Hence, protein synthesis is required for the action of this antibiotic. Metronidazole is reduced to the hydroxylamine derivative, which then binds to DMA, hence not requiring cell division or protein synthesis for its efficacy. PPIs do not synergize with this antibiotic. Resistance to metronidazole develops by decrease of the level of reducing enzyme and, therefore, may be relative or absolute. Resistance to clarithromycin occurs by a base mutation at the binding site on the RNA and is usually absolute. 

Reactions at the Hydroxylamine Nitrogen. These reagents have been used as 0-protected forms of hydroxylamine for synthetic transformations involving the unprotected nitrogen. Thus O-silylhydroxylamines have been used to prepare iV-hydroxy- 8-lactams and substituted dihydro-3-hydroxy-l,2,3-benzotria-zines, as weU as N-alkylated hydroxylamines for use as leuko-triene biosynthesis inhibitors. ... 

These novel metabolites may be derived from four amino acids tryptophan, anthranilic acid, valine, and alanine (or methylalanine). Deoxynor-tryptoquivalone (43) may be the first metabolite formed in the pathway of the tryptoquivaline biosynthesis. By oxidation of the secondary amine to the hydroxylamine, nortryptoquivalone (= tryptoquivalone) (32) would be formed from 43. If the isobutyl side chain is lost by further oxidation, tryptoquivaline J (39) and E (34) would be derived from these tryptoqui-valones, respectively. On the other hand, if reduction occurred on the carbonyl in the side chain, deoxynortryptoquivaline (42) and nortrypto-quivaline (FTD) (40) would be derived, respectively, from these tryptoqui-valones. The geminal dimethyl group at position 15 appeared to be formed by the participation of methylalanine in the biosynthesis, and the actual incorporation of " C-labeled methylalanine into tryptoquivaline (FTC) and tryptoquivaline I has been demonstrated (M. Yamazaki, unpublished work). 

Route b involves the synthesis of )S-cyanoalanine from cysteine and cyanide catalyzed by )9-cyanoalanine syntha% (EC 4.4.1.9), with the subsequent hydrolysis by ) -cyanoalanine hydrolase (EC 4.2.1.65). Both enzymes have been studied by Cooney et al. (1980) and Miller and Conn (1980). Cyanide may be liberated from the breakdown of cyanc enic glycosides (Conn, 1981 Nahr-stedt, 1987), the reaction of hydroxylamine and glycolate (Hucklesby et al., 1982), and during ethylene biosynthesis (Peiser et al., 1984). The possibility... 

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