Fructose-1-phosphate aldolase

Figure 10.14 Natural glycolytic substrates of the fructose 1,6-bisphosphate aldolase (FruA) and fructose 6-phosphate aldolase (FSA).

Functionally related to FruA is the novel class I fructose 6-phosphate aldolase (FSA) from E. coli, which catalyzes the reversible cleavage of fructose 6-phosphate (30) to give dihydroxyacetone (31) and d-(18) [90]. It is the only known enzyme that does not require the expensive phosphorylated nucleophile DHAP for synthetic purpose. 

Figure 6.8 Versatile one-pot synthesis of D-iminocyclitols with fructose-6-phosphate aldolase...

Schurmann, R. and Sprenger, G.A. (2001) Fructose-6-phosphate aldolase is a novel class I aldolase from Escherichia coli and is related to a novel group of bacterial transaldolases. The Journal of Biological Chemistry, 276, 11055-11061. 

Schurmann, M., Schurmann, M. and Sprenger, G.A. (2002) Fructose 6-phosphate aldolase and 1-deoxy-D-xy lulose 5-phosphate synthase from Escherichia coli as tools in enzymatic synthesis of 1-deoxysugars. Journal of Molecular Catalysis B, Enzymatic, 19, 247-252. 

Castillo, J.A., Calveras, J., Casas, J. et al. (2006) Fructose-6-phosphate aldolase in organic synthesis preparation of D-fagomine, /V-alkylated derivatives, and preliminary biological assays. Organic Letters, 8, 6067-6070. 

Sugiyama, M., Hong, Z.Y., Liang, RH. et al. (2007) D-Fructose-6-phosphate aldolase-catalyzed one-pot synthesis of iminocyclitols. Journal of the American Chemical Society, 129, 14811-14817. 

Fructose-6-Phosphate Aldolase An Alternative to DHAP-Dependent Aldolases ... 

Although fructose-6-phosphate aldolase (FSA) does not belong to the DHAP-dependent aldolases group, it deserves to be mentioned in this chapter as it can be considered as an alternative to those enzymes, or at least, an alternative to FBPA. FSA was described for the first time by Schiirmann and Sprenger in E. coli K-12 strain MG1655 [50]. The enzyme is a class I aldolase with a homodecameric... 

From the many enzymes that are known to make and break C-C bonds, we first chose the two transferases, transketolase (TKT) and transaldolase (TAL), both from the Gram-negative bacterium Escherichia coli. While project B21 evolved, we learned that this microorganism holds other and so far unknown enzymes which are of interest for asymmetric syntheses. One transketolase-like enzyme, 1-deoxy-D-xylulose 5-phosphate synthase (DXS), turned out to be the first enzyme of a novel biosynthetic pathway leading to isoprenoids in bacteria, algae, and plants. The other, fructose 6-phosphate aldolase (ESA) - while similar to transaldolase - allows the direct use of the inexpensive dihydroxyacetone in aldol condensations. 

Fig. 2.2.2.S Three-dimensional structures of transaldolase B (TAL B) and fructose 6-phosphate aldolase (FSA) from E. coli. a) TAL B forms a dimer structure b), c) FSA is a decameric enzyme consisting of two pentamer rings (right) one on top of the other, b) Two adjacent subunits of FSA showing the C-terminal extension of one...

D-Fructose-6-Phosphate Aldolase as Catalyst for Iminosugar Synthesis 307... 

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). 

Pig. 6.5.13 d-Fructose-6-phosphate aldolase (FSA) catalyzed aldol additions of DHA to a number of aldehyde acceptors... 

The (3S,4R) configured probes were prepared by enzymatic routes based on the stereospecific formation of a C-C bond catalyzed by either TK with Li-HPA as donor or by fructose-6-phosphate aldolase (FSA) Ref. [41]. The advantage of FSA for the synthesis of these probes is that acceptor substrates were commercially available, whereas a-hydroxylated TK acceptor substrates had to be prepared first by chemical routes [40, 41]. In particularly, the recently engineered FSA(A129S) variant that was optimized for dihydroxyacetone (DHA) as the donor substrate was found to be a powerful biocatalyst, leading to D-ketose analogs 16a and 16b with 67% and 77% yields, respectively. TK reactions furnished the same products but with lower yields only (37% and 47% respectively) (Scheme 15.17). 

The fructose 6-phosphate aldolase (ESA) from E. coli is a novel class I aldolase that catalyzes the reversible formation of fructose 6-phosphate from dihydroxyacetone and o-glyceraldehyde 3-phosphate it is, therefore, functionally related to transaldolases [245]. Recent determination of the crystal structure of the enzyme sho ved that it also shares the mechanistic machinery [246]. The enzyme has been sho vn to accept several aldehydes as acceptor components for preparative synthesis. In addition to dihydroxyacetone it also utilizes hydroxyacetone as an alternative donor to generate 1-deoxysugars, for example 118, regioselectively (Eigure 5.52) [247]. 

An exception is the dihydroxyacetone (DHA) utilizing aldolases such as the D-fructose-6-phosphate aldolase that also accepts hydroxyacetone, hydroxy-butanone, and glycoaldehyde. Such broad donor tolerance is almost unique among aldolases [8,82]. Aldolases can accept a broad structural variety of aldol acceptors, and this is what makes them highly important for synthetic applications. 

S. Schneider, T. Sandalova, C. Schneider, C.A. Sprenger, A.K. Samland, Replacement of a phenylalanine by a tyrosine in the active site confers fructose 6-phosphate aldolase activity to the transaldolase of Escherichia coli and human origin, I. Biol. Chem. 283 (2008) 30064-30072. 

A.L Concia, C. Lozano, J.A. Castillo, T. Patella, J. Joglar, P. Qapes, D-Fructose-6-phosphate aldolase in oiganic synthesis cascade chemical-enzymatic preparation of sugar-related poly-hydroxylated compounds, Chem. Eur. J. 15 (2009) 3808-3816. 

M. Gutierrez, T. Patella, J. Joglar, J. Bujons, P. Qapes, Strucmie-guided redesign of D-fructose-6-phosphate aldolase from E. coli remarkable activity and selectivity towards acceptor substrates by two-point mutation, Chem. Commun. 47 (2011) 5762-5764. 

DIHYDROXYACETONE PHOSPHATE (DHAP)-DEPENDENT ALDOLASES, d-FRUCTOSE-6-PHOSPHATE ALDOLASE (FSA) AND TRANSALDOLASES... 

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