2-Deoxy-d-ribose-5-phosphate aldolase (DERA): applications and modifications

Abstract

2-Deoxy-d-ribose-5-phosphate aldolase (DERA) is a class I aldolase that offers access to several building blocks for organic synthesis. It catalyzes the stereoselective C–C bond formation between acetaldehyde and numerous other aldehydes. However, the practical application of DERA as a biocatalyst is limited by its poor tolerance towards industrially relevant concentrations of aldehydes, in particular acetaldehyde. Therefore, the development of proper experimental conditions, including protein engineering and/or immobilization on appropriate supports, is required. The present review is aimed to provide a brief overview of DERA, its history, and progress made in understanding the functioning of the enzyme. Furthermore, the current understanding regarding aldehyde resistance of DERA and the various optimizations carried out to modify this property are discussed.

Cell-free synthetic biochemistry upgrading of ethanol to 1,3 butanediol

“…To convert acetaldehyde into 1,3-BDO we used the pathway developed by Yakunin and coworkers 19 – 21 . To join acetaldehyde to make 3-hydroxybutanal (3-HBal) we employ a promiscuous aldolase 2-deoxy- d -ribose-5-phosphate aldolase (DERA) 22 . DERA naturally catalyzes the reversible breakdown of 2-deoxy- d -ribose-5-phosphate to glyceraldehyde 3-phosphate and acetaldehyde.…”

The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis

“…In vivo it catalyses the synthesis of 2-deoxy-D-ribose-5-phosphate from acetaldehyde and glyceraldehyde-3-phosphate but in vitro it also catalyses the aldol reaction of acetaldehyde with numerous other simple aldehydes. 184 Its synthetic potential is limited by its low tolerance to industrially relevant aldehyde concentrations but this hurdle has been overcome by protein engineering. DSM, for example, developed a process for the synthesis of an advanced atorvastatin intermediate by aldol reaction of two equivalents of acetaldehyde with chloroacetaldehyde (Scheme 19b) that operates at 100 g L À1 substrate concentration.…”

Progress in Stereoselective Construction of C–C Bonds Enabled by Aldolases and Hydroxynitrile Lyases

“… General reaction mechanisms of class I (A) ( Haridas et al, 2018 ) and class II (B) aldolases ( Falcicchio et al, 2014 ). …”

“…Enzymes other than FSA can also generate polyols. 2-Deoxyribose 5-phosphate aldolase (DERA) is an acetaldehyde-dependent enzyme ( Haridas et al, 2018 ). It can accept three affinity substrates (propionaldehyde, acetone, and fluoropropane) as well as the natural nucleophilic substrate acetaldehyde, but the activities are lower than that of acetaldehyde ( Barbas et al, 1990 ; Chen et al, 1992 ; Wong et al, 1995 ).…”