GDP-mannose pyrophosphorylase

Sugiyama, T., Kido, N., Komatsu, T., Ohta, M., Jann, K., Jann, B., Saeki, A., Kato, N. Genetic analysis of Escherichia coli 09 rfb identification and DNA sequence of phos-phomannomutase and GDP-mannose pyrophosphorylase genes. Microbiology 140 (1994) 59-71. 

The alginate pathway and the activities of the alginate enzymes overlap with a few other metabolic endpoints. The committed step in alginate biosynthesis is the formation of GDP-mannuronate. GDP-mannose is the precursor of GDP-rhamnose, a constituent of the A-band in lipopolysaccharide (EPS). The GDP-mannose that is required for A-band EPS biosynthesis is formed by the action of phosphomannose isomerase (PMI)/GDP-mannose pyrophosphorylase (GMP) activities that are separate from those used in... 

Wong et al. previously reported a GDP-Man regeneration system starting from Man-l-P (53). However, as Fru-6-P is inexpensive, a new regeneration pathway has been developed by Wang et al. starting from Fru-6-P (Scheme 8). As shown in Scheme 8, the cycle comprises of three key enzymes phosphomannose isomer-ase (PMI, EC 5.3.1.8) for the conversion of Fru-6-P to Man-6-P (84-87), phosphomannose mutase (PMM, EC 5.4.2.8) for the conversion of Man-6-P to Man-l-P (88), and GDP-mannose pyrophosphorylase (GMP, EC 2.7.7.13) for condensation of Man-l-P with guanosine triphosphate to form GDP-Man (89-94). The recombinant bifunctional PMI/GMP from Helicobacter pylori has also been cloned and overexpressed in E. coli (95). 

Ning B, Elbein AD. Cloning, expression and characterization of the pig liver GDP-mannose pyrophosphorylase evidence that GDP-mannose and GDP-Glc pyrophosphorylases are different proteins. Eur J Biochem 2000 ... 

Ning B, Elbein AD. Purification and properties of mycobacterial GDP-mannose pyrophosphorylase. Arch Biochem Biophys 1999 362 339-345. 

Keller R, Springer F, Renz A, Kossmann J. Antisense inhibition of the GDP-mannose pyrophosphorylase reduces the ascorbate content in transgenic plants leading to developmental changes during senescence. Plant J 1999 19 131-141. 

Yoda K, Kawada T, Kaibara C, Fujie A, Abe M, Hashimoto H, Shimizu J, Tomishige N, Noda Y, Yamasaki M. Defect in cell wall integrity of the yeast Saccharomyces cerevisiae caused by a mutation of the GDP-mannose pyrophosphorylase gene VIG9. Biosci Biotechnol Biochem 2000 64 1937-1941. 

Agaphonov MO, Packeiser AN, Chechenova MB, Choi E-S, Ter-Avanesyan MD. Mutation of the homologue of GDP-mannose pyrophosphorylase alters cell wall structure, protein glycosylation and secretion in Hansenula polymor-pha. Yeast 2001 18 391-402. 

Davis AJ, Perugini MA, Smith BJ et al. Properties of GDP-mannose pyrophosphorylase, a critical enzyme and drug target in Leishmania mexicana. J Biol Chem 2004 279 12462-12468. 

GDP-mannose pyrophosphorylase (GMP, EC 2.7.7.13). The recombinant bifimctional PMI/GMP (phosphomannose isomerase/GDP-D-mannose pyrophosphorylase) from Helicobacter pylori has been cloned and overexpressed in E. coli (21), The bifunctional enzyme PMI/GMP catalyzes both the first and third steps of GDP-D-mannose biosynthesis from D-fructose-6-phosphate. In addition, PMM of H. pylori was also cloned and overexpressed (21), The system was coupled with a truncated al,2-mannosyltransferase (ManT catalytic domain, Saccharomyces cerevisiae) to synthesize the mannosyloligosaccharides (not published). 

Scheme 12. 1) Mannose phosphomutase 2) GDP-mannose pyrophosphorylase, GTP, pyrophosphatase.

The in vivo synthesis of GDP-mannose is equivalent to that of the UDP-sugars [29, 30] (see Scheme 12). Mannose-1-phosphate, prepared from maimose-6-phos-phate either by a phosphomutase reaction or chemically [61], is converted to GDP-mannose by a GDP-mannose pyrophosphorylase in the presence of GTP [86]. Also in this case a pyrophosphate side-product is generated which must be decomposed by a pyrophosphatase to shift the equilibrium to the desired GDP-Man. GDP-3-azido- and GDP-3-A-acetylmannose have also been obtained successfully by following this pathway [60]. 

We have cloned and overexpressed the enzymes phosphomannomutase (PMM, EC 5.4.2.8) and GDP-ot-D-mannose pyrophosphorylase (EC 2.7.7.13) from Salmonella enterica, group B, in E. coli [311], The partially purified... 

Fig. 16. Enzymatic synthesis of GDP-a-D-mannose (23) from D-mannose (20) via a-D-mannose-6-phosphate (21) and ot-D-mannose-1 -phosphate (22) with in situ regeneration of ATP. A Hexokinase (EC 2.7.1.1), B Pyruvate kinase (EC 2.7.1.40), C Phosphomannomutase (EC 5.4.2.8), D GDP-Man pyrophosphorylase (EC 2.7.7.13), E inorganic pyrophosphatase (EC 3.6.1.1) [311]...

The first steps in the pathway accomplish the synthesis of the nucleotide sugar that donates the monosaccharide units to the polymer. Fructose 6-phosphate is isomerized to mannose 6-phosphate the phosphoryl group is then transferred from the 6-position to the 1-position to generate mannose 1-phosphate. Mannose 1-phosphate and GTP are substrates for a pyrophosphorylase that catalyzes formation of GDP-mannose. GDP-mannose is oxidized to GDP-mannuronate in the final step that is catalyzed by a cytoplasmic enzyme. 

Thus, in the first group of bacteria, GDP-D-mannose inhibits its own synthesis by a simple feed-back inhibition. A similar mechanism is also operative in the second group, where GDP-L-fucose inhibits both GDP-D-mannose pyrophosphorylase and GDP-D-mannose oxi-doreductase. In the third group, where both sugar nucleotides are needed for polysaccharide synthesis, their biosynthesis is individually controlled, so that imbalance in the supply of these two sugars will not occur. 

Wu BY, Zhang Y-X, Zheng R, Guo C-W, Wang PG. Bifunctional phosphomannose isomerase/GDP-D-mannose pyrophosphorylase is the point of control for GDP-D-mannose biosynthesis in Helicobacter pylori. FEBS lett 2002 519 87-92. 

The regeneration of GDP-Man has been employed in the synthesis of mannose-based oligosaccharides (Scheme 11) [35]. GDP-Man can be produced from Man-1-P and GTP by the action of GDP-Man pyrophosphorylase (GDPMP EC 2.7.7.22) in a manner analogous to previously described for NDP-sugars. The system described employed an al,2-mannosyltransferase (al,2-ManT) that was overexpressed in E. coli. The al,2-ManT accepted mannose, mannobiose, and O-mannosyl gly-copeptides as substrates. 

Two routes to GDP-mannose have been explored a non-enzymatic one using essentially Schmidt chemistry, and an enzymatic one involving a hexokinase, a phosphomannomutase, and a pyrophosphorylase. Overall, preference was given to the chemical approach, which was also applied to the synthesis of GDP-galactose, GDP-xylose, and GDP-2-acetamido-2-deoxy-D-glucose. ... 

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