Discovery, Engineering, and Synthetic Application of Transaminase Biocatalysts

Abstract

Transaminases have attracted considerable interest in their use as biocatalysts for the synthesis of compounds containing chiral amine units, which are widespread within the pharmaceutical, agrochemical, and fine chemical industry. Recent developments in enzyme- and process-engineering have expedited their use in asymmetric synthesis; however, industrial applications are still hindered by a number of factors, including equilibrium thermodynamics, product inhibition, and poor substrate tolerance. Detailed and comprehensive approaches to each of these challenges have been reported during the last two decades; the most representative enzyme discovery and screening strategies, protein and equilibrium engineering, and immobilization techniques are reviewed herein. Furthermore, we present a detailed look into the applications of transaminases for the synthesis of a variety of amine-containing compounds and the integration of transaminases into multienzymatic systems that allow access to a variety of highly complex products for the end user.

Sequential Two‐Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases

“…At this point the bio‐transamination experiments with (3 E )‐4‐(het)arylbut‐3‐en‐2‐ones 2 a – p were assayed, in order to identify not only acceptable reaction conditions but also suitable amine transaminases (ATAs) for each substrate, so that the stereoselective amination of the racemic alcohols might be attempted later in a concurrent approach. Pyridoxal‐5′‐phosphate (PLP)‐dependent ATAs have been found to be ideal biocatalysts for the transformation of prochiral and racemic ketones into optically active amines by using a molar excess of an amine donor, generally isopropylamine or alanine . For simplicity, an initial assessment was developed with ketone 2 a and the commercially available R ‐selective ATA‐024, which is known to accept isopropylamine as amine donor.…”

Biocatalytic Production of Amino Carbohydrates through Oxidoreductase and Transaminase Cascades

“…[38,39] This makes biocatalytic production of amines from alcohols highly desirable,y et challenging,b ecause no known single enzyme can catalyzes uch a transformation, and the chemical or chemo-enzymatic methods involving oxidation and reductive amination often involve toxic chemicals and requirec omplicated synthetic procedures. [41,[43][44][45] In this context, enzymatic pathways from primary and secondary alcohols to the corresponding amines,b yu tilizing oxidases or alcohold ehydrogenases coupled with an w-TA, have been demonstrated. [41,[43][44][45] In this context, enzymatic pathways from primary and secondary alcohols to the corresponding amines,b yu tilizing oxidases or alcohold ehydrogenases coupled with an w-TA, have been demonstrated.…”

Three‐liquid‐phase Spinning Reactor for the Transaminase‐catalyzed Synthesis and Recovery of a Chiral Amine

“…Due to a theoretical yield of 100 %, the asymmetric synthesis is often preferred . However, physical and chemical strategies for counteracting the unfavourable thermodynamic equilibrium and/ or product inhibition are needed . Besides the use of an excess of amine donor (AD), methods such as co‐product or product cyclization or polymerization, evaporation of the volatile co‐product and enzymatic cascades for co‐product removal have been developed.…”