2-deoxy-D-ribose-5-phosphate aldolase DERA

Another promising route was reported in patent and open hterature by both DSM and Diversa [13, 14]. This route employs a 2-deoxy-D-ribose 5-phosphate aldolase (DERA) that catalyzes a tandem aldol addition in which two equivalents of acetaldehyde (AA) are added in sequence to chloroacetaldehyde (CIAA) to produce a lactol derivative that is similar to the 3,5-dihydoxy side chain of synthetic statins (Figure 6.2e). Diversa screened environmental libraries for novel wild-type DERAs and identified an enzyme that was both tolerant to increased substrate concentrations and more active than DERA from E. coli in the target reaction [13]. 

Deoxy-D-Ribose 5-Phosphate Aldolase (DERA)-Based Routes to... 

To date, 2-deoxy-D-ribose 5-phosphate aldolase (DERA) is the only acetaldehyde-dependent aldolase being applied in organic synthesis. Thus the stereoselectivity of DERA is significant, all known enzymes from different organisms showing the same preferences, limiting the field of application to syntheses in which specifically the DERA-catalyzed enantiomer is needed. 

An economically viable alternative to the synthesis of deoxyribonuclosides has been developed as a two stage process involving 2-deoxy-D-ribose 5-phosphate aldolase (DERA) (Fig. 6.5.14) (Tischer et al. 2001). The first step was the aldol addition of G3P to acetaldehyde catalyzed by DERA. G3P was generated in situ by a reverse action of EruA on L-fructose-1,6-diphosphate and triose phosphate isomerase which transformed the DHAP released into G3P. In a second stage, the action of pentose-phosphate mutase (PPM) and purine nucleoside phosphorylase (PNP), in the presence of adenine furnished the desired product. The released phosphate was consumed by sucrose phosphorylase (SP) that converts sucrose to fructose-1-phosphate, shifting the unfavorable equilibrium position of the later reaction. 

Deoxy-D-ribose 5-phosphate aldolase (DERA) catalyzes in vivo the reversible aldol addition of acetaldehyde to D-glyceraldehyde-3-phosphate to furnish 2-deoxy-n-ribose 5-phosphate (Scheme 10.30). 

The 2-deoxy-D-ribose 5-phosphate aldolase (RibA or DERA EC 4.1.2.4) is a class I enzyme that in vivo catalyzes the reversible addition of ethanal to D-glyceraldehyde... 

Figure 6.2 Overview of biocatalytic routes to vastatin side chains. PLE pig-liver esterase, ADH alcohol dehydrogenase, HHDH halohydrin dehalogenase, DERA 2-deoxy-D-ribose 5-phosphate aldolase.

The 2-deoxy-D-ribose 5-phosphate aldolase (RibA or DERA EC 4.1.2.4) is a class I enzyme that, in vivo, catalyzes the reversible addition of acetaldehyde to D-glyceraldehyde 3-phosphate (34 Figure 5.57) in the metabolic degradation of 127 from deoxyribonucleosides [269], ivith an equilibrium constant for synthesis of 2 x lO m [56]. It is, therefore, unique among the aldolases in that it uses an aldehyde rather than a ketone as the aldol donor. RibA has been isolated from eukaryotic and prokaryotic sources [270, 271],... 

Deoxy-D-ribose-5-phosphate aldolase (RibA or DERA)... 

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