Application of α-keto acid decarboxylases in biotransformations

• Published in: Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular Enzymology 1998-06, Vol.1385 (2), p.307-322
• Main Authors: Iding, H., Siegert, P., Mesch, K., Pohl, M.
• Format: Article
• Language: English
• Subjects: Acetoin; Amino Acid Sequence; Benzoylformate decarboxylase; Biotransformation; Carboxy-Lyases - chemistry; Carboxy-Lyases - genetics; Carboxy-Lyases - metabolism; Decarboxylation; Keto Acids - chemistry; Keto Acids - metabolism; Ketones - chemical synthesis; Molecular Sequence Data; Mutagenesis, Site-Directed; Phenylacetyl carbinol; Pyruvate decarboxylase; Pyruvate Decarboxylase - chemistry; Pyruvate Decarboxylase - genetics; Pyruvate Decarboxylase - metabolism; Site-directed mutagenesis; Stereoisomerism; Substrate Specificity; Thiamin diphosphate; α-Hydroxy ketone; α-Keto acid decarboxylase
• ISSN: 0167-4838; 0006-3002; 1879-2588
• DOI: 10.1016/S0167-4838(98)00076-4

The advantages of using enzymes in the synthesis of organic compounds relate to their versatility, high reaction rates, and regio- and stereospecificity and the relatively mild reaction conditions involved. Stereospecificity is especially important in the synthesis of bioactive molecules, as only one of the enantiomeric forms usually manifests bioactivity, whereas the other is often toxic. Although enzymes which catalyze asymmetric carbon-carbon bond formation are of great importance in bioorganic chemistry, only a few examples are known for thiamin diphosphate (ThDP)-dependent enzymes, whereas transformations using e.g. aldolases, lipases and lyases are well documented already. The present review surveys recent work on the application of pyruvate decarboxylase and benzoylformate decarboxylase in organic synthesis. These enzymes catalyze the synthesis of chiral α-hydroxy ketones which are versatile building blocks for organic and pharmaceutical chemistry. Besides the substrate spectra of both enzymes amino acid residues relevant for substrate specificity and enantioselectivity of pyruvate decarboxylase have been investigated by site-directed mutagenesis.