Lyase and Process for Asymmetric Synthesis of (S)-Phenylacetylcarbinol

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes engineered lyase enzymes capable of producing (S)-phenylacetylcarbinol (S-PAC) with exceptionally high enantiomeric purity (up to 98% ee) via an asymmetric synthesis from inexpensive, non-chiral starting materials such as benzaldehyde and pyruvate or acetaldehyde. The invention involves specific mutations in the enzyme from Acetobacter pasteurianus, substituting isoleucine at position 468 and optionally tryptophan at position 543 with smaller amino acids, enhancing selectivity and effectiveness. The patent covers the enzymes, DNA sequences encoding them, suitable vectors, as well as processes for in vivo (whole-cell biocatalysis) and in vitro production of S-PAC.

Use CasesContent extracted from patent full text and abstract with AI.

• Industrial production of (S)-phenylacetylcarbinol for use as a chiral building block in fine chemical and pharmaceutical synthesis.
• Manufacturing of active pharmaceutical ingredients (APIs) that require high enantiopurity starting materials.
• Biocatalytic production processes in the chemical and biotech industry, reducing reliance on traditional chemical synthesis.
• Production of S-PAC as an intermediate for drugs such as ephedrine and pseudoephedrine.
• Bioprocess development platforms for academic and contract research organizations working on chiral synthesis.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables highly efficient and selective synthesis of (S)-phenylacetylcarbinol, with enantiomeric excesses up to 98%.
• Reduces or eliminates the need for costly and wasteful chiral resolution or separation steps.
• Utilizes cheap, easily-available achiral starting materials, lowering production costs.
• Prevents formation of undesirable byproducts and regioisomers, simplifying purification.
• Applies both to whole-cell and cell-free (enzyme) processes, enabling flexible manufacturing options.
• Facilitates greener and more sustainable production methods versus traditional chemical syntheses.
• Offers genetic tools (DNA, vectors) for easy implementation in a range of host organisms such as E. coli, Corynebacteria, or yeast.

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Inventors & Applicants

Patent Abstract

The invention relates to a lyase and to a method for asymmetric synthesis of (S)-phenylacetylcarbinol. According to the invention, a lysase is provided in which the isoleucine is substituted at position no. 468 in the protein ApPDC-E469G, which is modified in comparison to the wild type protein from Aceobacter pasteurianus, with an amino acid that occupies less space than isoleucine. In an advantageous embodiment, the amino acid tryptophan in position no. 543 of the enzyme according to the invention is replaced by a different amino acid that occupies less space than tryptophan. The enzymes according to the invention can be used for asymmetric synthesis of (S)-phenylacetylcarbinol. Enantiomeric excesses of up to 98 % ee can thereby be achieved.