Fuculose 1-phosphate aldolase

W. D. Fessner, G. Sinerius, A. Schneider, M. Dreyer, G. E. Schulz, J. Badia, and J. Arguilar, Diastereoselective enzymatic aldol additions L-Rhamnulose and L-fuculose 1-phosphate aldolases from E. coli, Angew. Chem, lnt. Ed. Engl. 30 555 (1991). 

Fig. 3. Schematic representation of substrate binding and C-C bond formation for the class II fuculose 1-phosphate aldolase from Escherichia coli...

Table 5. Substrate tolerance of L-rhamnulose 1-phosphate and L-fuculose 1-phosphate aldolases [195,347]...

Concerning aldolases, the cloning of enzymes is becoming more and more common. Thus the bacterial fuculose-1-phosphate aldolase (EC 4.1.2.17) and 2-deoxyribose-5-phosphate aldolase (EC 4.1.2.4) have been recently overexpressed in E. coli and their synthetic use has been examined.115,116... 

Water-in-oil gel emulsions were tested in enzymatic aldolization of selected N-Cbz-amino aldehydes (Figure 19.3), N-Cbz-3-amino propanal (4), N-Cbz-glycinal, (5), (S)-N-Cbz-alaninal (6), and (R)-N-Cbz-alaninal (7) catalyzed by RAMA and L-rham-nulose-1-phosphate aldolase (RhuA) and L-fuculose-1-phosphate aldolase (FucA) from Escherichia coU [27,28]. The largest differences between conventional dimethyl formamide (DMF)/water co-solvent systems and gel emulsions were observed with RAMA and FucA catalysts (Figure 19.3). The emulsion media enhanced the catalytic efficiency of RAMA towards the N-Cbz amino aldehydes tested three, five. 

One of the most efficient methods for the generation of 2,5-dideoxy-2,5-iminogalactitol 16 relies on the fuculose-1-phosphate aldolase-catalyzed aldol condensation of 2-azido-3-hydroxypropanal with dihydroxyacetone monophosphate (Scheme 13.17). The same method, applied to (2/ )-2-azidopropanal R)-V7 and to (25 )-2-azido-propanal (5 )-17, allows for the preparation of 2,5,6-trideoxy-2,5-imino-D-allitol 18 and 2,5,6-trideoxy-2,5-imino-L-talitol 19, respectively [22]. 

Figure 13-7 Interaction of the bound zinc ion of L-fuculose-1-phosphate aldolase and catalytic side chains with the substrate in the active site of the enzyme as revealed by X-ray crystallography and modeling. See Dreyer and Schulz. ...

NaBH4 reduction with the help of CeCl3 -7H20 to obtain threo derivatives 232 (O Scheme 61). An enzymatic route for the synthesis of L-fucose analogs modified at the non-reducing end is reported by Fessner et al. [86], Using 2-Hydroxy-2-methylpropanal 233 and dihydroxyacetone phosphate 234 as substrates, branched fucose derivative 237 has been prepared via recombinant L-fuculose 1-phosphate aldolase (FucA) and L-fucose ketol isomerase (Fuel) in E. coli (O Scheme 62). 

Examples of chemoenzymatic synthesis of 2,5-dideoxy-2,5-iminoalditols based on fuculose-1-phosphate aldolase-catalyzed aldol reactions. 

Fessner et al.[256] developed an efficient method for the synthesis of L-fucose analogs modified at the nonpolar terminus by means of L-fucose isomerase and l-fuculose 1-phosphate aldolase from E. coli. Various L-fucose analogs bearing linear or branched aliphatic side chains were prepared in about 30% overall yield with hydroxyaldehyde precursors and dihydroxyacetone phosphate as the starting materials (Fig. 17-32). 

CA provides the best-defined example of an ionized Zn -bound water mechanism. " Thrl99 and orientation residues such as Glul06, and proton shuttle residues such as His64, are needed to make CA the fastest biological catalyst. 6-Pyruvoly-tetrahydropterin synthase,E. coli fuculose-1-phosphate aldolase, " " and E. coli fructose-1,6-bisphosphate aldolase belong to the CA family, although the reactions these enzymes are involved in are different. 

E. coli fuculose-1-phosphate aldolase HiS 3 1 HiSa, 60 Hisb (C) H2O GIul 84-86... 

The four enzymes of the family of dihydroxyacetone phosphate (DHAP)-dependent aldolases fructose-1,6-bisphosphate aldolase (FruA, EC 4.1.2.13), fuculose-1-phosphate aldolase (FucA, EC 4.1.2.17), rhamnulose-1-phosphate aldolase (RhuA, EC 4.1.2.19) and tagatose-1,6-bisphosphate aldolase (TagA, EC 4.1.2.40), catalyze in vivo the reversible asymmetric addition of DHAP to d-glyceraldehyde-3-phosphate (G3P) or L-lactaldehyde, leading to four complementary diastereomers. DHAP-dependent aldolases create two new stereogenic centers, with excellent enantio and diastereoselectivity in many cases. These enzymes are quite specific for the donor substrate DHAP, but accept a wide range of aldehydes as acceptor substrates. There are only two fructose-6-phosphate aldolase isoenzymes reported to be able to use dihydroxyacetone (DHA) as donor substrate (Schiirmann and Sprenger 2001). 

These systems were tested in the enzymatic aldolization of a variety of A/-Cbz-aminoaldehydes catalyzed by D-fructose-l,6-bisphosphate aldolase from rabbit muscle (RAMA) and L-rhamnulose-1-phosphate aldolase and L-fuculose-1-phosphate aldolase from E. coli (Espelt et al. 2003 a,b, 2005). The largest differences between conventional DMF/water cosolvent systems and gel emulsions were observed with RAMA catalyst (Fig. 6.5.11). 

Ardao I, Benaiges MD, Caminal G et al. (2006) One step purificationAmmobilization of fuculose-1-phosphate aldolase, a class II dependent aldolase, by using mettil-chelate supports. Enzyme... 

Fuculose 1-Phosphate Aldolase. Another potential route to different stereochemistries at C3 and C4 is via different aldolases. Of the four possible diastereomers that can result from an aldol condensation between DHAP and an electrophile, aldolases have been identified in Nature that stereoselectively generate three (Scheme 6). 

The uses of fuculose-1-phosphate aldolase in the preparation of l,5-dideoxy-l,5-diamino-D-talitol and 1-deoxygalactostatin have been described. ... 

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