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Biomedical subjects

Herfried Griengl

Publications and source records attributed to Herfried Griengl.

6 recordsLinked to original sources
PubMed2007

Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using "thio-disguised" precursors and oxynitrilase catalysis.

3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.

Aldehyde-Lyases↗
PubMed2005

Stereoselective hydroxylation of an achiral cyclopentanecarboxylic acid derivative using engineered P450s BM-3.

Substrate engineered, achiral carboxylic acid derivative was biohydroxylated with various mutants of cytochrome P450 BM-3 to give two out of the four possible diastereoisomers in high de and ee. The BM-3 mutants exhibit up to 9200 total turnovers for hydroxylation of the engineered substrate, which without the protecting group is not transformed by this enzyme.

Bacterial Proteins↗
PubMed2002

The use of substrate engineering in biohydroxylation.

In the biohydroxylation of nonactivated carbon atoms, substrate engineering has been found to be a very useful and simple means to influence substrate acceptance and the regioselectivity and stereoselectivity of this transformation. Recently, this methodology has been applied to the hydroxylation of a large number of compounds including cycloalkane carboxylic acids, ketones, amines, amides and alcohols.

Bacteria↗
PubMed2002

Oxidative biotransformations using oxygenases.

Considerable progress has been made in manipulating oxidative biotransformations using oxygenases. Substrate acceptance, catalytic activity, regioselectivity and stereoselectivity have been improved significantly by substrate engineering, enzyme engineering or biocatalyst screening. Preparative biotransformations have been carried out to synthesize useful pharmaceutical intermediates or chiral synthons on the gram to several-hundred-gram scale, by use of whole cells of wild type or recombinant strains. The synthetic application of oxygenases in vitro has been shown to be possible by enzymatic or electrochemical regeneration of NADH or NADPH.

Biotransformation↗
PubMed1999

In situ proton-NMR analyses of Escherichia coli HB101 fermentations in 1H2O and in D2O.

Experiments using one-dimensional Fourier-transform proton-NMR spectrometry for non-invasive analyses of microbial fermentations in situ, in vivo and in normal aqueous buffer are described. Analyses of the 'mixed acid' fermentation during growth of Escherichia coli on glucose and citrate were performed to identify and quantitatively estimate the concentrations of the two substrates provided and of the six products formed without sampling from the NMR tube. Identification of fermentation substrates and products was achieved by coincidence of selected diagnostic proton signals of individual compounds in the same solvent. The complete time course of growth of E. coli in the NMR tube correlated well with that of the same culture grown outside the magnet, with samples taken for proton-NMR analyses. The entire course of these in situ proton measurements during growth over 16-24 h was obtained automatically, usually unattended overnight. Thus, the utilization and formation of eight substances in the fermentation were monitored simultaneously, in normal 1H2O, without sampling and individual analysis. Several metabolic changes could be readily detected during the fermentations. Additionally, the pH changes were estimated from the chemical shifts of the acetate signal as growth progressed. The effect of varying D2O concentrations in the solvent on growth rates and product yields was examined, and the increase in the complexity of signals given by these fermentations is described. This versatile and rapid method for the simultaneous, direct and automatic analysis of mixtures of many compounds has the potential to be extended to routine on-line analyses of industrial fermentations.

Citric Acid↗