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DERA-Catalyzed Chemoenzymatic Access to Nucleobase-Substituted Candidate Statin Precursors

Journal Article (2026)
Author(s)

Romina Fernández Varela (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

E.M.M. Abdelraheem (Student TU Delft)

Lautaro Giaimo (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

Luciano Cortés (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

Leticia Lafuente (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

Ana Laura Valino (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

P.L. Hagedoorn (TU Delft - BT/Biocatalysis)

U. Hanefeld (TU Delft - BT/Biocatalysis)

Adolfo Iribarren (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

Elizabeth Lewkowicz (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

Research Group
BT/Biocatalysis
DOI related publication
https://doi.org/10.3390/biom16020321
More Info
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Publication Year
2026
Language
English
Research Group
BT/Biocatalysis
Journal title
Biomolecules
Issue number
2
Volume number
16
Article number
321
Downloads counter
12
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Abstract

Aldolases are powerful biocatalysts for the stereoselective formation of carbon–carbon bonds and are widely used in the synthesis of chiral intermediates for pharmaceutical applications. Among them, 2-deoxyribose-5-phosphate aldolase (DERA) has been extensively exploited for the preparation of the conserved side chain of statins. In this work, we report a novel chemoenzymatic approach for the synthesis of nucleobase-substituted lactol products as potential precursors of new statin analogues. A C49M variant of DERA from Pectobacterium atrosepticum (PaDERA C49M) was employed to catalyze sequential aldol additions using aldehyde-functionalized nucleobases as non-natural electrophilic substrates. The formation of nucleobase-containing lactols was confirmed, demonstrating for the first time the acceptance of nucleobase-derived aldehydes in DERA-catalyzed aldol reactions. This strategy provides access to structurally novel statin side-chain precursors and expands the synthetic potential of DERA toward the generation of new classes of bioactive compounds.