000131796 001__ 131796
000131796 005__ 20240731103415.0
000131796 0247_ $$2doi$$a10.1021/acscatal.3c02615
000131796 0248_ $$2sideral$$a137063
000131796 037__ $$aART-2023-137063
000131796 041__ $$aeng
000131796 100__ $$aGrajales-Hernández, Daniel A.
000131796 245__ $$aSpatial organization of immobilized multienzyme systems improves the deracemization of alkyl glyceryl ethers
000131796 260__ $$c2023
000131796 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131796 5203_ $$aProduction of enantiomerically pure molecules is of utmost importance in the pharma industry. In this context, biocatalysis emerges as an alternative to conventional chemical methods due to the exquisite selectivity and specificity underlying the enzymes. In this work, we design a multienzymatic system to perform the deracemization of alkyl glyceryl ethers as potential building blocks for the synthesis of drugs. The key to success in this route is controlling the spatial organization of the enzymes involved in the cascade through their immobilization on porous carriers. By fine tuning the intraparticle organization of an enzymatic cascade comprising an (S)-selective glycerol dehydrogenase from Bacillus stearothermophilus and an (R)-selective ketoreductase from Lactobacillus kefir, we performed the oxidoreductive deracemization of rac-alkyl/aryl glyceryl ethers with a yield up to 100% and enantiomeric excess e.e. > 99%, otherwise impossible using a soluble system. Remarkably, we find that optimal spatial assembly of the biocatalyst ameliorates the inhibition phenomena experimented by the system and increases the deracemization rate by 4-fold. Finally, integrating an enzymatic nicotinamide adenine dinucleotide oxidized disodium salt (NAD+) regeneration system to the heterogeneous biocatalyst, we intensified the process by reusing it in discontinuous and consecutive batch cycles and scaling the reaction up to 250 mM substrate, achieving 100% yield and e.e. > 99%.
000131796 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E37-23R$$9info:eu-repo/grantAgreement/ES/MINECO/PID2021-125762NB-I00
000131796 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000131796 590__ $$a11.3$$b2023
000131796 592__ $$a3.847$$b2023
000131796 591__ $$aCHEMISTRY, PHYSICAL$$b23 / 178 = 0.129$$c2023$$dQ1$$eT1
000131796 593__ $$aChemistry (miscellaneous)$$c2023$$dQ1
000131796 593__ $$aCatalysis$$c2023$$dQ1
000131796 594__ $$a20.8$$b2023
000131796 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000131796 700__ $$aDiamanti, Eleftheria
000131796 700__ $$aMoro, Riccardo
000131796 700__ $$0(orcid)0000-0001-9478-6750$$aVelasco-Lozano, Susana
000131796 700__ $$0(orcid)0000-0002-2676-8814$$aPires, Elisabet$$uUniversidad de Zaragoza
000131796 700__ $$aLópez-Gallego, Fernando
000131796 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000131796 773__ $$g13, 23 (2023), 15620-15632$$pACS catal.$$tACS CATALYSIS$$x2155-5435
000131796 8564_ $$s949932$$uhttps://zaguan.unizar.es/record/131796/files/texto_completo.pdf$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2024-11-20
000131796 8564_ $$s925960$$uhttps://zaguan.unizar.es/record/131796/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint$$zinfo:eu-repo/date/embargoEnd/2024-11-20
000131796 909CO $$ooai:zaguan.unizar.es:131796$$particulos$$pdriver
000131796 951__ $$a2024-07-31-10:06:20
000131796 980__ $$aARTICLE