{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:04:21Z","timestamp":1771653861293,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009559","name":"Universidad Nacional de Quilmes","doi-asserted-by":"crossref","award":["PP I+D 2287\/22"],"award-info":[{"award-number":["PP I+D 2287\/22"]}],"id":[{"id":"10.13039\/501100009559","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, ANPCYT","doi-asserted-by":"crossref","award":["PICT 2019 1361"],"award-info":[{"award-number":["PICT 2019 1361"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica, ANPCYT","doi-asserted-by":"crossref","award":["PICT 2021 0984"],"award-info":[{"award-number":["PICT 2021 0984"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Council of Science and Technology, CONICET","award":["11220200101081CO"],"award-info":[{"award-number":["11220200101081CO"]}]},{"name":"ERACoBiotech","award":["053.80.737"],"award-info":[{"award-number":["053.80.737"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aldolases are powerful biocatalysts for the stereoselective formation of carbon\u2013carbon 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.<\/jats:p>","DOI":"10.3390\/biom16020321","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:51:09Z","timestamp":1771491069000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DERA-Catalyzed Chemoenzymatic Access to Nucleobase-Substituted Candidate Statin Precursors"],"prefix":"10.3390","volume":"16","author":[{"given":"Romina","family":"Fern\u00e1ndez Varela","sequence":"first","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9008-2729","authenticated-orcid":false,"given":"Eman","family":"Abdelraheem","sequence":"additional","affiliation":[{"name":"Biocatalysis Group, Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lautaro","family":"Giaimo","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano","family":"Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-0449","authenticated-orcid":false,"given":"Leticia","family":"Lafuente","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Laura","family":"Valino","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-2022","authenticated-orcid":false,"given":"Peter-Leon","family":"Hagedoorn","sequence":"additional","affiliation":[{"name":"Biocatalysis Group, Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4102-6165","authenticated-orcid":false,"given":"Ulf","family":"Hanefeld","sequence":"additional","affiliation":[{"name":"Biocatalysis Group, Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Iribarren","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-6271","authenticated-orcid":false,"given":"Elizabeth","family":"Lewkowicz","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotransformaciones y Qu\u00edmica de \u00c1cidos Nucleicos, Universidad Nacional de Quilmes, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Roque S. Pe\u00f1a 352, Bernal B1876BXD, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5334\/gh.1278","article-title":"World Heart Federation Roadmap for Secondary Prevention of Cardiovascular Disease: 2023 Update","volume":"19","author":"Laranjo","year":"2024","journal-title":"Glob. 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