Process considerations for the asymmetric synthesis of chiral amines using transaminases

Abstract

Biocatalytic transamination is being established as key tool for the production of chiral amine pharmaceuticals and precursors due to its excellent enantioselectivity as well as green credentials. Recent examples demonstrate the potential for developing economically competitive processes using a combination of modern biotechnological tools for improving the biocatalyst alongside using process engineering and integrated separation techniques for improving productivities. However, many challenges remain in order for the technology to be more widely applicable, such as technologies for obtaining high yields and productivities when the equilibrium of the desired reaction is unfavorable. This review summarizes both the process challenges and the strategies used to overcome them, and endeavors to describe these and explain their applicability based on physiochemical principles. This article also points to the interaction between the solutions and the need for a process development strategy based on fundamental principles.

Mechanism‐Guided Engineering of ω‐Transaminase to Accelerate Reductive Amination of Ketones

“…[1] To harness the full capacity of biocatalysts as synthetic toolkits,e nzyme properties such as stability,s ubstrate range and optimal reaction conditions should be compatible with amanufacturing setting. [2] However, the design of ab iocatalytic process is often limitedb ys ophisticated enzyme properties evolved for biological fitness that is incongruous with industrial demands.…”

Evaluation of Diffusion Coefficient Determination using a Microfluidic Device

“…On the other hand, acetophenone is an interesting substrate for asymmetric synthesis of chiral amines catalyzed by omega transaminases. 25 The reaction is very difficult to carry out owing to the unfavorable thermodynamic equilibrium and severe product inhibition. In addition, acetophenone is only slightly soluble in water and for increasing its solubility a co-solvent is needed.…”

Transaminases and their Applications

“…Furthermore, unusual amino acids, for example, β-amino acids, deployed in peptidomimetics, offer higher stability against proteases. For the synthesis of unnatural amino acids or bulky amines, novel ω-transaminases are used [3][4][5][6][7]. Several synthesis strategies were established and optimized for transaminases, facing the challenges of product and substrate inhibition and the need to shift the equilibrium toward the product.…”

“…Reactions catalyzed by transaminases offer advantages like a promiscuous substrate spectrum, no need for external cofactors, high enantio-and stereoselectivity, mild reactions conditions, and good reaction yields. Only catalytic amounts of PLP, as described in Section 29.2.4, are needed as a cofactor to stabilize and to form the active dimer [4,6,29,33].…”