title: From amino alcohol to aminopolyol: one-pot multienzyme oxidation and aldol addition.
abstract: In this work, the successful coupling of enzymatic oxidation and aldol addition reactions for the synthesis of a Cbz-aminopolyol from a Cbz-amino alcohol was achieved for the first time in a multienzymatic one-pot system. The two-step cascade reaction consisted of the oxidation of Cbz-ethanolamine to Cbz-glycinal catalyzed by chloroperoxidase from the fungus Caldariomyces fumago and aldol addition of dihydroxyacetone phosphate to Cbz-glycinal catalyzed by rhamnulose-1-phosphate aldolase expressed as a recombinant enzyme in Escherichia coli, yielding (3R,4S)-5-{[(benzyloxy)carbonyl]amino}-5-deoxy-1-O-phosphonopent-2-ulose. Tools of enzymatic immobilization, reactor configurations, and modification of the reaction medium were applied to highly increase the production of the target compound. While the use of soluble enzymes yielded only 23.6 % of Cbz-aminopolyol due to rapid enzyme inactivation, the use of immobilized ones permitted an almost complete consumption of Cbz-ethanolamine, reaching Cbz-aminopolyol yields of 69.1 and 71.9 % in the stirred-tank and packed-bed reactor, respectively. Furthermore, the reaction production was 18-fold improved when it was catalyzed by immobilized enzymes in the presence of 5 % (v/v) dioxane, reaching a value of 86.6 mM of Cbz-aminopoliol (31 g/L).
authors.affiliation: Applied Biocatalysis Unit Associated to IQAC-UAB-CSIC, Department of Chemical Engineering, School of Engineering, Universitat Autònoma de Barcelona, 08193 Bellaterra-Cerdanyola del Vallès, Catalonia, Spain.
authors.forename: Milja
authors.initials: M
authors.lastname: Pešić
authors.forename: Carmen
authors.initials: C
authors.lastname: López
authors.forename: Josep
authors.initials: J
authors.lastname: López-Santín
authors.forename: Gregorio
authors.initials: G
authors.lastname: Alvaro
mesh_terms: D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000605:Amino Alcohols / Q000378:metabolism*; D001203:Ascomycota / Q000201:enzymology / Q000235:genetics; D001709:Biotechnology / Q000379:methods; D002711:Chloride Peroxidase / Q000235:genetics / Q000378:metabolism*; D004800:Enzymes, Immobilized / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D010084:Oxidation-Reduction; D011108:Polymers / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D000605:Amino Alcohols; D004800:Enzymes, Immobilized; D011108:Polymers; C024617:polyol; C116609:3-hydroxybutanal; D002711:Chloride Peroxidase; D000446:Aldehyde-Lyases; C022526:rhamnulose-1-phosphate adolase