Guanosine triphosphate biosynthesis

These organisms have been used frequently in the elucidation of the biosynthetic pathway (37,38). The mechanism of riboflavin biosynthesis has formally been deduced from data derived from several experiments involving a variety of organisms (Fig. 5). Included are conversion of a purine such as guanosine triphosphate (GTP) to 6,7-dimethyl-8-D-ribityUuma2ine (16) (39), and the conversion of (16) to (1). This concept of the biochemical formation of riboflavin was verified in vitro under nonen2ymatic conditions (40) (see Microbial transformations). 

The biosynthesis processes of purines, pterins, and flavins are closely related. Both pterins and flavins are synthesized via the guanosine triphosphate (GTP) purine intermediate. 

There are a number of studies on the biosynthesis of various pteridines, i.e., xanthopterin (65), isoxanthopterin (67), erythropterin (73), leucopterin (68), and pterin (62) (509-511). The most important intermediate of the proposed biosynthetic pathway from guanosine triphosphate (GTP) (604) seems to be di-hydroneopterin triphosphate (H2-NTP) (605), however, because evidence has recently been accumulated indicating that pteridines such as biopterin (70), sepiapterin (81), and drosopterins (87) are synthesized from GTP (604) by way of H2-NTP (605) (Scheme 76) (5/2). 

The biosynthesis of riboflavin, from the nucleotide guanosine triphosphate (GTP), requires at least six enzymatic activities and is subject to a complex regulation architecture [136, 139]. The genes that encode the enzymes have been identified and cloned [136]. 

The precursors for riboflavin biosynthesis in plants and microorganisms are guanosine triphosphate and ribulose 5-phosphate. As shown in Figure 7.3, the first step is hydrolytic opening of the imidazole ring of GTP, with release of carbon-8 as formate, and concomitant release of pyrophosphate. This is the same as the first reaction in the synthesis ofpterins (Section 10.2.4), but utilizes a different isoenzyme of GTP cyclohydrolase (Bacher et al., 2000, 2001). 

The biosynthesis of molybdopterin is outlined in Fig. 19. The initial step involves rearrangement of guanosine triphosphate to precursor Z. Sulfur transfer followed by metallation and guanylation gives the cofactor. 

Guanosine triphosphate and ribulose-5-phosphate are recruited in a 1 2 stoichiometric ratio by GTP cyclohydrolase II and DHBP synthase, respectively, for riboflavin biosynthesis. Since at substrate saturation the activity of B. subtilis DHBP is twice the activity of B. suhtilis cyclohydrolase II (DSM, unpublished observations) and since both enzymatic activities are associated with the same bifunctional protein encoded by rihA, the balanced formation of the pyrimidinedione and the dihydroxybutanone intermediates is ensured. However, the ifg.s constant of DHBP synthase ( 1 mmol is about 100-fold higher than the ifg.s constant of GTP cyclohydrolase II imposing the risk of excessive synthesis of the pyrimidinone and pyrimidinedione intermediates in case of reduced intracellular concentrations of pentose phosphate pathway intermediates. This can be expected, for instance, in glucose-limited fed-batch fermentations, which are frequentiy used in industrial applications. The pyrimidinone and pyrimidinedione intermediates are highly reactive, oxidative compounds, which can do serious damage on the bacteria. 

This chapter gives an overview of the biosynthesis of THF, (6if)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4), and molybdopterin (MPT), the organic compound of the molybdenum cofactor (Moco), and discusses the enzymoiogy of the proteins that bind the three classes of cofactors (structures are shown in Scheme 1). The biosynthesis of THF, BH4, and MPT start from guanosine triphosphate (GTP), but the reactions for the conversion of GTP into the three cofactors are diverse and involve different enzymatic compounds. 

CjHiiNsOj, Mr 237.22. The (l J ,2 S) form (L-erythro form) form ale yellow cryst., mp. 250-280 C (decomp.), [a]o-66 (0.1 m HCI), pK, 2.23, pK 2 7.89. In alkaline solution B. shows blue fluorescence. It is widely distributed in microorganisms, insects (e.g. in royaI jelly of queen bees), algae, amphibians, and mammals and is also found in urine. In metabolism tet-rahydro-B. acts as a cofactor for phenylalanine 4-monooxygenase (EC 1.14.16.1). B. is a growth factor for insects. The (l /, 2 /f) form (D-threo form) known as dictyopterin melts at >300 C and has pK , 2.20, pKa2 7.92. It occurs in the slime mold Dictyostelium discoideum. The biosynthesis starts from guanosine triphosphate. 

Riboflavin biosynthesis [301] in prokaryotes starts from guanosine triphosphate and ribulose-5-phosphate in a 1-2M ratio, respectively (Figure 7.5). The hydrolytic opening of the imidazole ring of GTP (RibA cyclohydrolase II reaction) is followed by (i) deamination of the resulting pyrimidinone to afford... 

Other nucleoside triphosphates, which are energetically equivalent to ATP, are important in some metabolic reactions cytidine triphosphate in phospholipid biosynthesis, guanosine triphosphate in protein biosynthesis and oxidative decarboxylation of 2-oxoacids (see Thcarboxylic acid cycle), inosine triphosphate in certain carboxylations, uridine triphosphate in polysaccharide biosythesis. 

The biosynthesis of adenosine and guanosine triphosphates proceeds by phosphorylation of the low energy monophosphate precursors. For example, GTP may be synthesized from guanosine monophosphate (GMP), at the expense of two ATP molecules ... 

The chemical synthesis of adenosine and guanosine triphosphate may be undertaken in a fashion analogous to their biosynthesis phosphorylation of the low energy monophosphate precursors. Phosphorylation is accomplished with phosphoric acid and a coupling (dehydrating) agent, DCC. Use of carbodiimides has already been discussed in connection with peptide bond formation. It will be recalled that reaction proceeds by way of an anhydride... 

In addition to their role as components of nucleoproteins, purines and pyrimidines are vital to the proper functioning of the cell. The bases are constituents of various coenzymes, such as coenzyme A (CoA), adenosine triphosphate (ATP), guanosine triphosphate (GTP), cytidine triphosphate (CTP), diphosphopyridine nucleotide (DPN), triphosphopyridine nucleotide (TPN), and flavin adenine dinucleotide (FAD). A pyrimidine derivative, cytidine diphosphate choline, is involved in phospholipid synthe another pyrimidine compound, uridine diphosphate glucose, is an important substance in carbohydrate metabolism. Cytidine diphosphate ribitol functions in the biosynthesis of a new group of bacterial cell-wall components, the teichoic acids. While mammals excrete nitrogen derived from protein catabolism in the form of urea, birds eliminate their nitrogen by synthesizing it into the purine compound, uric acid. 

Microbial biosynthesis of riboflavin from the precursor guanosine triphosphate (GTP) and D-ribulose 5-phosphate occurs through seven enzymatic steps, which have been reviewed previously (Bacher et al. 2000). 

GTP Guanosine triphosphate, a nucleotide serving as a switch in many important processes including protein biosynthesis and signal transduction. 

Biosynthesis of 7,8-didemethyl-8-hydroxy-5-deazaflavin starts from guanosine-5 -triphosphate (GTP), which leads through several steps to 5-amino(6-ribitylamino)-2,4( 1 //,3//)-pyrimidinedione 5 -phosphate, whose addition to 4-hydroxybenzoic acid which comes from shikimate gave the target compound <85JA8300>. The biosynthesis of riboflavin and deazaflavins has been studied in Methanobacterium thermoautotrophicum <91JBC9622>. 

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