Biosynthesis of Vitamin B₂: A Unique Way to Assemble a Xylene Ring

Abstract

The biosynthesis of one riboflavin (vitamin B(2)) molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. In the final step, the tricyclic isoalloxazine chromophore, which is the hallmark of flavocoenzymes, arises from a highly unusual dismutation of bicyclic 6,7-dimethyl-8-ribityllumazine that is catalyzed by riboflavin synthase but can also proceed without catalysis. The reaction proceeds via a pentacyclic adduct of two 6,7-dimethyl-8-ribityllumazine molecules, whose cleavage into riboflavin and a pyrimidine derivative (by a sequence of two elimination steps) is mechanistically straightforward. Recently, the formation of the pentacyclic adduct has been proposed to involve a hydride transfer step followed by a [4+2] cycloaddition. Surprisingly, two different classes of riboflavin synthases utilize different diastereomers of the pentacyclic adduct, but the newly generated chiral centers are lost upon the intermediates' subsequent fragmentation.

A comparative genomics perspective on the genetic content of the alkaliphilic haloarchaeon Natrialba magadii ATCC 43099T

“…Most bacteria, fungi, and plants can synthesize riboflavin de novo using one molecule of GTP and two molecules of ribulose 5-phosphate as substrates [74]. Riboflavin biosynthesis has been described in M jannaschii [75]. In general, reduction precedes deamination in the archaeal riboflavin biosynthesis pathway, which appears to be similar to the fungal pathway.…”

“…In general, reduction precedes deamination in the archaeal riboflavin biosynthesis pathway, which appears to be similar to the fungal pathway. In M. jannaschii , GTP cyclohydrolase III, the first enzyme of the riboflavin biosynthesis pathway, produces an archaeal-specific formylated intermediate that requires a subsequent deformylation step [75]. However, the haloarchaeal homolog of GTP cyclohydrolase III has not been identified thus far.…”

One Protein, Two Chromophores: Comparative Spectroscopic Characterization of 6,7-Dimethyl-8-ribityllumazine and Riboflavin Bound to Lumazine Protein

“…Key for the assignment of proton hfcs is the comparison of samples measured in protonated and deuterated buffers and the electron-spin density maps obtained from DFT calculations. Three types of protons, namely, the ones attached to C(7α) and the two protons attached to N (3) and N (5), are supposed to be acidic and, thus, susceptible to deuterium exchange. With this knowledge at hand, the hfcs of all protons attached to the spin system could be unambiguously assigned ( Table 2).…”

A novel bifunctional transcriptional regulator of riboflavin metabolism in Archaea

“…The riboflavin biosynthesis pathway (RBP) includes a set of committed enzymes that produce one riboflavin molecule from one molecule of Guanosine triphosphate (GTP) and two molecules of ribulose 5-phosphate (Figure 1) (6). In Bacteria, these enzymes include RibA, RibB, the bifunctional deaminase/reductase RibD, as well as RibH and RibE, involved in the final two steps of RBP (Table 1).…”