72599-80-5Relevant articles and documents
Convergent in situ Generation of Both Transketolase Substrates via Transaminase and Aldolase Reactions for Sequential One-Pot, Three-Step Cascade Synthesis of Ketoses
Lorillière, Marion,Guérard-Hélaine, Christine,Gefflaut, Thierry,Fessner, Wolf-Dieter,Clapés, Pere,Charmantray, Franck,Hecquet, Laurence
, p. 812 - 817 (2019/12/27)
We describe an efficient three-enzyme, sequential one-pot cascade reaction where both transketolase substrates are generated in situ in a convergent fashion. The nucleophilic donor substrate hydroxypyruvate was obtained from l-serine and pyruvate by a transaminase-catalyzed reaction. In parallel, three different (2S)-α-hydroxylated aldehydes, l-glyceraldehyde, d-threose, and l-erythrose, were generated as electrophilic acceptors from simple achiral compounds glycolaldehyde and formaldehyde by d-fructose-6-phosphate aldolase catalysis. The compatibility of the three enzymes was studied in terms of temperature, enzyme ratio and substrate concentration. The efficiency of the process relied on the irreversibility of the transketolase reaction, driving a shift of the reversible transamination reaction and securing the complete conversion of all substrates. Three valuable (3S,4S)-ketoses, l-ribulose, d-tagatose, and l-psicose were obtained in good yields with high diastereoselectivity.
Broadening deoxysugar glycodiversity: Natural and engineered transaldolases unlock a complementary substrate space
Rale, Madhura,Schneider, Sarah,Sprenger, Georg A.,Samland, Anne K.,Fessner, Wolf-Dieter
supporting information; experimental part, p. 2623 - 2632 (2011/04/16)
The majority of prokaryotic drugs are produced in glycosylated form, with the deoxygenation level in the sugar moiety having a profound influence on the drug's bioprofile. Chemical deoxygenation is challenging due to the need for tedious protective group manipulations. For a direct biocatalytic de novo generation of deoxysugars by carboligation, with regiocontrol over deoxygenation sites determined by the choice of enzyme and aldol components, we have investigated the substrate scope of the F178Y mutant of transaldolase B, TalBF178Y, and fructose 6-phosphate aldolase, FSA, from E. coli against a panel of variously deoxygenated aldehydes and ketones as aldol acceptors and donors, respectively. Independent of substrate structure, both enzymes catalyze a stereospecific carboligation resulting in the D-threo configuration. In combination, these enzymes have allowed the preparation of a total of 22 out of 24 deoxygenated ketose-type products, many of which are inaccessible by available enzymes, from a [3 -8] substrate matrix. Although aliphatic and hydroxylated aliphatic aldehydes were good substrates, D-lactaldehyde was found to be an inhibitor possibly as a consequence of inactive substrate binding to the catalytic Lys residue. A 1-hydroxy-2-alkanone moiety was identified as a common requirement for the donor substrate, whereas propanone and butanone were inactive. For reactions involving dihydroxypropanone, TalBF178Y proved to be the superior catalyst, whereas for reactions involving 1-hydroxybutanone, FSA is the only choice; for conversions using hydroxypropanone, both TalBF178Y and FSA are suitable. Structure-guided mutagenesis of Ser176 to Ala in the distant binding pocket of TalBF178Y, in analogy with the FSA active site, further improved the acceptance of hydroxypropanone. Together, these catalysts are valuable new entries to an expanding toolbox of biocatalytic carboligation and complement each other well in their addressable constitutional space for the stereospecific preparation of deoxysugars.
