FSA-Catalyzed Carboligation: New Synthetic Opportunities from an Ancient Enzyme Scaffold
Abstract
Aldol reactions constitute a powerful methodology for carbon-carbon bond formation in synthetic organic chemistry. Biocatalytic carboligation offers a green, uniquely regio- and stereoselective tool to perform this transformation. New enzymes from the transaldolase scaffold, such as fructose-6-phosphate aldolase (FSA) from E. coli, were recently shown to be unusually flexible in their substrate scope,[1] which renders them particularly valuable for the synthesis of complex polyfunctional targets.[2] So far, wild-type FSA has been demonstrated to utilize dihydroxypropanone, hydroxypropanone, 1-hydroxybutanone, and hydroxyethanal as aldol donor components for highly stereoselective carboligation reactions. In this work we demonstrate the utility of rational protein engineering to design variant FSA mutant proteins (FSA*) that offer an extended tolerance for donor substrate modifications towards the creation of novel products that are of commercial interest.[3]
References
[1] Rale, M.; Schneider, S.; Sprenger, G. A.; Samland, A. K.; Fessner, W.-D. Chem. Eur. J. 2011, 17, 2623-2632 [2] Samland, A. K.; Rale, M.; Sprenger, G. A.; Fessner, W.-D. ChemBioChem 2011, 14, in press (DOI: 10.1002/chem.201002942) [3] (a) Castillo, J. A.; Calveras, J.; Casas, J.; Mitjans, M.; Vinardell, M. P.; Parella, T.; Inoue, T.; Sprenger, G. A.; Joglar, J.; Clapés, P. Org. Lett. 2006, 8, 6067-6070; (b) Garrabou, X.; Castillo, J. A.; Guerard-Helaine, C.; Parella, T.; Joglar, J.; Lemaire, M.; Clapes, P. Angew. Chem., Int. Ed. 2009, 48, 5521-5525; (c) Castillo, J. A.; Guerard-Helaine, C.; Gutierrez, M.; Garrabou, X.; Sancelme, M.; Schuermann, M.; Inoue, T.; Helaine, V.; Charmantray, F.; Gefflaut, T.; Hecquet, L.; Joglar, J.; Clapes, P.; Sprenger, G. A.; Lemaire, M. Adv. Synth. Catal. 2010, 352, 1039-1046.
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