Biocatalytic approaches for the quantitative production of single stereoisomers from racemates

Abstract

Strategies for the chemoenzymatic transformation of a racemate into a single stereoisomeric product in quantitative yield have been developed. A range of industrially relevant α-hydroxycarboxylic acids was deracemized in a stepwise fashion via lipase-catalysed enantioselective O-acylation, followed by mandelate racemase-catalysed racemization of the remaining non-reacted substrate enantiomer. Alternatively, aliphatic α-hydroxycarboxylic acids were enzymatically isomerized using whole resting cells of Lactobacillus spp. Enantioselective hydrolysis of rac-sec-alkyl sulphate esters was accomplished using novel alkyl sulphatases of microbial origin. The stereochemical path of catalysis could be controlled by choice of the biocatalyst. Whereas Rhodococcus ruber DSM 44541 and Sulfolobus acidocaldarius DSM 639 act through inversion of configuration, stereo-complementary retaining sulphatase activity was detected in the marine planctomycete Rhodopirellula baltica DSM 10527.

Beyond the bacterium: planctomycetes challenge our concepts of microbial structure and function

“…It possesses genes that putatively encode enzymes for standard chemoheterotrophic pathways (for example, heterolactic fermentation), as well as 110 genes that encode products with homology to the sulphatases of bacteria and eukaryotes and that might have a role in the degradation of sulphated glyco polymers such as those in marine-snow aggregates. These sulphatases could be useful as industrial catalysts 99,100 . Transcriptomic studies indicated that these sulphatases may also be involved in the formation of disulphide bridges in cell wall proteins 101 .…”

Life cycle analysis of the model organism Rhodopirellula baltica SH 1T by transcriptome studies

“…For instance, the genome harbours enzymes for the synthesis of complex organic molecules with possible applications in the pharmaceutical field, such as a gene set encoding a polyketide synthase, and enzymes important for the production of natural products in the food or animal‐feed industry, such as those active in vitamin and amino acid biosynthesis. The application of sulfatases of R. baltica for the stereoselective conversion of racemates has been discussed in Wagner and Horn (2006) and Gadler and colleagues (2006). Many of the genes are unique and may be employed to enhance the efficiency of microbial strains already in biotechnical use.…”

Epoxide hydrolase-mediated enantioconvergent bioconversions to prepare chiral epoxides and alcohols

“…This process, referred to as kinetic resolution, is still one of the major methods for industrial productions of chiral compounds (Breuer et al 2004). In order to obtain yields greater than 50%, three approaches have been considered: (1) asymmetric synthesis from prochiral substrates; (2) dynamic kinetic resolution (DKR) of racemates; (3) enantioconvergent process (Gadler et al 2006;Lee 2007;Strauss et al 1999). In DKR, resolution is combined with rapid in situ racemization where the less reactive enantiomer is rapidly converted to the more reactive enantiomer so that the equilibrium of two enantiomers is constantly readjusted.…”