Deoxyribose-phosphate aldolase (DERA)

Deoxyribose-phosphate aldolase (DERA) is a class I aldolase enzyme (EC 4.1.2.4) that catalyzes the reversible aldol cleavage and condensation of 2-deoxy-D-ribose 5-phosphate, primarily yielding D-glyceraldehyde-3-phosphate and acetaldehyde[1][2][3]. Functionally, it plays a role in a branch of the pentose phosphate pathway, supplying key intermediates to glycolysis and the Krebs cycle, and is inducible in bacteria for utilization of exogenous deoxyribonucleosides[1]. In humans, DERA is highly expressed in lungs, liver, and colon, where it contributes to stress responses by supporting energy production under metabolic or oxidative stress conditions[1][2]. DERA’s unique ability to accept small aldehydes as both donor and acceptor in aldol reactions makes it industrially valuable for stereoselective C–C bond formation, especially in the enzymatic synthesis of pharmaceuticals such as nucleoside analogs (e.g., islatravir) and statin side chains[1][2]. A key challenge for biotechnological application is DERA’s low tolerance to high aldehyde concentrations, as it is inactivated by reactive intermediates that accumulate during industrial reactions. Protein engineering efforts aim to overcome these limitations and expand its substrate scope and stability[2].

Other names

DeoxyriboaldolasePhosphodeoxyriboaldolase2-deoxyribose-5-phosphate aldolase2-deoxy-D-ribose 5-phosphate aldolase2-deoxy-D-ribose-5-phosphate acetaldehyde-lyaseDEOCCGI-26

Catalyzes C–C bond formation/cleavage between aldehyde substrates (via Schiff base intermediate with lysine at the active site); drug synthesis utilizes its enantioselective aldol reaction capability[1][2]