(R)-Selective Transaminases for Enantioselective Amine Synthesis
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Solution Overview
Problem
There is a need for additional stereoselective transaminases to broaden the applicability of stereoselective transamination reactions to a wider range of compounds, as existing (R)-selective enzymes are scarce compared to (S)-selective enzymes, limiting the synthesis of enantiomerically enriched (R)-amines from ketones.
Innovation Solution
Identification and utilization of novel transaminases with at least 90% identity to specific amino acid sequences, isolated from various microorganisms, which exhibit (R)-selective ω-transaminase activity, enabling the enzymatic synthesis of enantiomerically enriched (R)-amines from corresponding ketones.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If (S)-selective transaminases are used for biocatalytic production of chiral amines, then the reaction can proceed efficiently with abundant enzyme availability, but the product obtained is the (S)-enantiomer rather than the desired (R)-enantiomer
Solution Approach 1:
The invention changes the stereoselectivity parameter of the transaminase enzyme by using (R)-selective transaminases instead of the more common (S)-selective enzymes. This parameter change in enzyme specificity allows the same biocatalytic transamination reaction to produce (R)-amines with high enantiomeric excess, resolving the contradiction between enzyme availability and desired product configuration.
2Manufacturing precision
If existing (R)-selective transaminases are used, then the desired (R)-amines can be produced, but the scope of applicable substrates is limited
Solution Approach 1:
The invention achieves universality by discovering and applying (R)-selective transaminases from multiple microbial sources that can catalyze the transamination of diverse ketone substrates. The patent demonstrates that these enzymes can process various aromatic and aliphatic ketones, thereby expanding the substrate scope while maintaining high (R)-selectivity, making the method broadly applicable to different amine production needs.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These novel transaminases achieve high enantiomeric excess (up to 99%) in the production of (R)-amines, expanding the scope of compounds that can be synthesized through stereoselective transamination reactions.
Implementation Method 1
The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c] from the corresponding ketones of the general formula (1)[a] by using novel transaminases
Data Source
AI summary
The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c]from the corresponding ketones of the general formula [1][a]by using novel transaminases.These novel transaminases are selected from two different groups: either from a group of some 20 proteins with sequences as specified herein, or from a group of proteins having transaminase activity and isolated from a microorganism selected from the group of organisms consisting of Rahnella aquatilis, Ochrobactrum anthropi, Ochrobactrum tritici, Sinorhizobium morelense, Curtobacterium pusiffium, Paecilomyces lilacinus, Microbacterium ginsengisoli, Microbacterium trichothecenolyticum, Pseudomonas citronellolis, Yersinia kristensenii, Achromobacter spanius, Achromobacter insolitus, Mycobacterium fortuitum, Mycobacterium frederiksbergense, Mycobacterium sacrum, Mycobacterium fluoranthenivorans, Burkhoideria sp., Burkhoideria tropica, Cosmospora episphaeria, and Fusarium oxysporum.