Acetohydroxyacid synthase: A new enzyme for chiral synthesis of R-phenylacetylcarbinol

• Published in: Biotechnology and bioengineering Vol. 83; no. 7; pp. 833 - 840
• Main Authors: Engel, Stanislav, Vyazmensky, Maria, Geresh, Shimona, Barak, Ze'ev, Chipman, David M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 30.09.2003; Wiley
• Subjects: acetolactate synthase; Acetolactate Synthase - metabolism; Acetone - analogs & derivatives; Acetone - chemical synthesis; Acetone - chemistry; Acetone - isolation & purification; benzaldehyde; Benzaldehydes; Binding Sites; biocatalysis; Biological and medical sciences; Biotechnology; Catalysis; chiral; enantiomeric excess; Enzyme engineering; Escherichia coli - enzymology; Escherichia coli - genetics; Fermentation; Fundamental and applied biological sciences. Psychology; hydroxyketone; Isoenzymes - metabolism; Methods. Procedures. Technologies; Miscellaneous; Molecular Structure; pyruvate; pyruvate decarboxylase; Pyruvic Acid; Stereoisomerism; stereospecificity; Temperature; thiamin diphosphate; Time Factors; chiral; Enzyme; thiamin diphosphate; Benzaldehyde; Lyases; enantiomeric excess; pyruvate; biocatalysis; Biocatalyst; Oxo-acid-lyases; Carbon-carbon lyases; Carboxy-lyases; Chirality; Acetolactate synthase; Stereospecificity; hydroxyketone; Pyruvate decarboxylase
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.10728

We have found that acetohydroxyacid synthase (AHAS) is an efficient catalyst for the enantiospecific (≥98% enantiomeric excess) synthesis of (R)‐phenylacetylcarbinol (R‐PAC) from pyruvate and benzaldehyde, despite the fact that its normal physiological role is synthesis of (S)‐acetohydroxyacids from pyruvate and a second ketoacid. (R)‐phenylacetylcarbinol is the precursor of important drugs having α and β adrenergic properties, such as L‐ephedrine, pseudoephedrine, and norephedrin. It is currently produced by whole‐cell fermentations, but the use of the isolated enzyme pyruvate decarboxylase (PDC) for this purpose is the subject of active research and development efforts. Some of the AHAS isozymes of Escherichia coli have important advantages compared to PDC, including negligible acetaldehyde formation and high conversion of substrates (both pyruvate and benzaldehyde) to PAC. Acetohydroxyacid synthase isozyme I is particularly efficient. The reaction is not limited to condensation of pyruvate with benzaldehyde and other aromatic aldehydes may be used. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 833–840, 2003.