Riboflavin, 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). 

Lumazine, l,3-dimethyl-6-phenyl-oxidation, 3, 305 Lumazine, 6,7-dimethyl-8-ribityl-in riboflavin biosynthesis, 1, 93 Lumazine, 6,7-dimethyl-8-D-ribityl-biosynthesis, 3, 320 structure, 3, 277 Lumazine, 6,7-dimethyl-2-thio-reactions... 

Pyrimidin-5-amine, 2,4-dioxy-6-ribitylamino-in riboflavin biosynthesis, 1, 93 Pyrimidin-5-amine, 2-methyI-in thiamin biosynthesis, 1, 99 Pyrimidin-5-amine, 4-methyl-synthesis, 3, 130... 

The pathway which is now thought to be involved in riboflavin biosynthesis by microorganisms is outlined in Scheme 9. The role of a purine derivative as an early precursor was... 

The final step in riboflavin biosynthesis has been extensively investigated. Incorporation and degradation studies with synthetic (33) using cell-free systems and purified enzymes have shown that two molecules of (33) are utilized to afford one molecule of riboflavin and one molecule of (36). Significantly, the lumazine (33) labelled at the C-6 methyl with deuterium is converted to riboflavin labelled at C-5 and in the C-7 methyl. Based on this and kinetic and spectroscopic data, Plaut has proposed a detailed mechanism for the riboflavin synthetase reaction (B-71MI10402). It is noteworthy that this reaction can also be accomplished non-enzymatically under neutral conditions with the same stereospecificity observed in the enzymic reaction (69CC290). 

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 Retrobiosynthetic Method Evolved in the Context of Studies on Riboflavin Biosynthesis... 

Mechanistic studies on the formation of the molybdopterin cofactor are still at an early stage. Conversion of guanosine, presumably as the triphosphate, to precursor Z occurs with retention of C-8 [84]. A possible mechanism for this third type of cyclohydrolase, which is consistent with the labeling experiment, is outlined in Fig. 20. (The other two types of cyclohydrolase are cyclohydrolase 1 for folate biosynthesis and cyclohydrolase II for riboflavin biosynthesis. In both cases, C8 is removed as formate.)... 

RIB2 DRAP deaminase, catalyzes the third step of the riboflavin biosynthesis... 

Riboflavin Biosynthesis Genes as Potential Drug Targets 28... 

Earlier work on riboflavin biosynthesis has been reviewed repeatedly. The present article is focused on recent work on the structure and mechanism of riboflavin biosynthetic enzymes. For historic aspects of this research area, the reader is directed to review the articles cited. 

Figure 4 Proposed reaction mechanism for reduction of the ribosyiamino to the ribityiamino moiety in riboflavin biosynthesis.

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