Conversion of Aldoses to Valuable ω-Amino Alcohols Using Amine Transaminase Biocatalysts

Abstract

The conversion of readily available monosaccharides to high-value amino alcohols using a key biocatalytic step is an attractive strategy for the preparation of these chiral synthons. Here, we report a previously undescribed example of the direct amination of monosaccharides, which exist predominantly in their cyclic form at equilibrium, using amine transaminase biocatalysts, providing access to a panel of amino alcohols in moderate to high conversion and isolated yield. A recently developed high-throughput colorimetric screen, employing o-xylylenediamine, was initially used to identify amine transaminase enzymes displaying this activity towards cyclic sugars and reactions were successfully scaled-up using isopropylamine.

The crystal structure of the tetrameric DABA‐aminotransferase EctB, a rate‐limiting enzyme in the ectoine biosynthesis pathway

“…In this study, we present the first crystal structure and biochemical characterization of the DABA aminotransferase EctB in the ectoine biosynthesis pathway, of the well‐studied osmoadaptation organism C. salexigens DSM 3043. The EctB enzyme from C. salexigens serves as a benchmark enzyme for further annotation of the poorly characterized DABA aminotransferases, and future design of better biocatalysts for either increased production of ectoine, or potentially the synthesis of valuable amine bonds at the distal ω‐position of substrates [1,62] that may be accepted by EctB from C. salexigens . Herein, we present a detailed investigation of EctB’s oligomeric state and describe how dimerization is important for shaping the active site.…”

“…Furthermore, we notice that there is a positive charge conservation among the DABA aminotransferases at position 155 (R/K) that helps stabilize the tetrameric interface. increased production of ectoine, or potentially the synthesis of valuable amine bonds at the distal x-position of substrates [1,62] that may be accepted by EctB from C. salexigens. Herein, we present a detailed investigation of EctB's oligomeric state and describe how dimerization is important for shaping the active site.…”

Catalytic amidation of natural and synthetic polyol esters with sulfonamides

“…For example, erythritol, xylitol, and sorbitol are all well-known sugar-derived polyols, as well as tough targets for biomass conversion 42–44 . Sugar-derived aminopolyols are also potentially useful molecules in drug discovery because of their structural resemblance to carbohydrates, and they are extensively studied synthetic targets 45–50 . In our strategy, all hydroxyl groups of erythritol, xylitol, and sorbitol were first fully acetylated, and the resulting esters ( 1p , 1q , and 1r ) were subjected to the standard catalytic sulfonamidation conditions with saccharin.…”

Direct monitoring of biocatalytic deacetylation of amino acid substrates by 1H NMR reveals fine details of substrate specificity

“…33,34 Furthermore, 1 H NMR spectroscopy has been used to measure biocatalysed reactions; examples include lipase-catalysed acylations 35 and monophosphates ring opening reactions, 36 determination of the % ee of hydrolytic KRs, 37,38 and to characterise complex carbohydrate derivatives. 39,40 Here we report the development, optimization and application of a novel 1 H NMR assay to monitor amide hydrolysis catalysed by a highly active deacetylase (Scheme S1D †). This was achieved by direct observation (both time dependent and end-point) of the sharp, well-resolved singlet peak associated with the methyl group of the acetate product.…”