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A Multidisciplinary Approach Toward the Rapid and Preparative-Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase-/omega-Transaminase-Mediated Synthesis of (2S,3S)-2-Aminopentane-1,3-diol

Smith, MEB; Chen, BH; Hibbert, EG; Kaulmann, U; Smithies, K; Galman, JL; ... Micheletti, M; + view all (2010) A Multidisciplinary Approach Toward the Rapid and Preparative-Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase-/omega-Transaminase-Mediated Synthesis of (2S,3S)-2-Aminopentane-1,3-diol. ORG PROCESS RES DEV , 14 (1) 99 - 107. 10.1021/op900190y.

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Abstract

Chiral amino alcohols represent an important class of value-added biochemicals and pharmaceutical intermediates. Chemical routes to such compounds are generally step intensive, requiring environmentally unfriendly catalysts and solvents. This work describes a multidisciplinary approach to the rapid establishment of biocatalytic routes to chiral aminodiols taking the original synthesis of (2S,3S)-2-aminopentane-1,3-diol as a specific example. An engineered variant of Escherichi coli transketolase (D469T) was used for the initial asymmetric ynthesis of (3S)-1,3-dihydroxypentan-2-one from the achiral substrates propanal and hydroxypyruvate. A bioinformatics led strategy was then used to identify and clone an omega-transaminase from Chromobacterium violaceum (DSM30191.) capable of converting the product of the transketolase-catalysed step to the required (2S,3S)-2-aminopentane-1,3-diol using isopropylamine as an inexpensive amine donor. Experiments; to characterize, optimize and model the kinetics of each reaction step were performed at the 1 mL scale using previously established automated microwell processing techniques. The microwell results, provided excellent predictions of the reaction kinetics when the. bioconversions were subsequently scaled up to preparative scales in batch stirred-tank reactors. The microwell methods thus provide process chemists and engineers with a valuable tool for the rapid and early evaluation of potential synthetic strategies. Overall, this work describes a concise and efficient biocatalytic route to chiral amino alcohols and illustrates an integrated multidisciplinary approach to bioconversion process design and scale-up.

Type:Article
Title:A Multidisciplinary Approach Toward the Rapid and Preparative-Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase-/omega-Transaminase-Mediated Synthesis of (2S,3S)-2-Aminopentane-1,3-diol
DOI:10.1021/op900190y
Keywords:ESCHERICHIA-COLI TRANSKETOLASE, D-ERYTHRO-SPHINGOSINE, DIRECTED EVOLUTION, STEREOSELECTIVE-SYNTHESIS, SUBSTRATE-SPECIFICITY, OMEGA-TRANSAMINASES, ENZYME, SERINE, DIHYDROSPHINGOSINE, AMINOTRANSFERASE
UCL classification:UCL > School of BEAMS > Faculty of Engineering Science > Biochemical Engineering
UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry

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