Verena Resch

Karl-Franzens-Universität Graz | KFU Graz · Department of Biorganic and Renewable Resources

Imine reductases (IREDs) have recently become a primary focus of research in biocatalysis, complementing other classes of amine‐forming enzymes such as transaminases and amine dehydrogenases. Following in the footsteps of other research groups, we have established a set of IRED biocatalysts by sequence‐based in silico enzyme discovery. In this stud...

The acyl transferase from Mycobacterium smegmatis (MsAcT) catalyses transesterification reactions in aqueous media because of its hydrophobic active site. Aliphatic cyanohydrin and alkyne esters can be synthesised in water with excellent and strikingly opposite enantioselectivity [( R );E>37 and ( S );E>100, respectively]. When using this enzyme, t...

In order to extend the applicability of the regioselective enzymatic carboxylation of phenols, the substrate scope of o ‐benzoic acid (de)carboxylases has been investigated towards complex molecules with an emphasis on flavouring agents and polyphenols possessing antioxidant properties. o ‐Hydroxycarboxylic acid products were obtained with perfect...

Supplementary

Organofluorine compounds have become important building blocks for a broad range of advanced materials, polymers, agrochemicals, and increasingly for pharmaceuticals. Despite tremendous progress within the area of fluorination chemistry, methods for the direct introduction of fluoroalkyl-groups into organic molecules without prefunctionalization ar...

Supplementary Figures 1-55, Supplementary Tables 1-21, Supplementary Methods, and Supplementary References.

Acyltransferase from Mycobacterium smegmatis (MsAcT) immobilised in continuous-flow microchannel (30-50 μm dia.) reactors with hierarchical pore structure (4 cm3/g total pore volume) enabled quantitative, full and rapid transesterification of neopentylglycol with ethyl acetate in a biphasic 50/50 % system in less than one minute. MsAcT was attached...

to unsaturated lactones and ketones using whole cells of a Rhodococcus strain

Review: selectivity and applicability of the different catalytic approaches for the direct addition of water to C=C double bonds; 130 refs.

The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enan...

Water is omnipresent and essential. Yet at the same time it is a rather unreactive molecule. The direct addition of water to C=C double bonds is therefore a challenge not answered convincingly. In this perspective we critically evaluate the selectivity and the applicability of the different catalytic approaches for water addition reactions, homogen...

Chemo-enzymatic deracemisation was applied to obtain the (S)-enantiomer of 1-benzylisoquinolines from the racemate in high isolated yield (up to 85%) and excellent optical purity (ee > 97%). The one-pot deracemisation protocol encompassed enantioselective oxidation by a monoamine oxidase (MAO-N) and concomitant reduction of the resulting iminium sp...

All 20 proteinogenic amino acids are screened for this reaction.

Deracemization, that is, the transformation of a racemate into a single product enantiomer with theoretically 100 % conversion and 100 % ee, is an appealing but also challenging option for asymmetric synthesis. Herein a novel chemo-enzymatic deracemization concept by a cascade is described: the pathway involves two enantioselective oxidation steps...

Deracemisierung, also die Umwandlung eines Racemats in ein enantiomerenreines Produkt mit theoretisch 100 % Ausbeute und 100 % ee, stellt eine attraktive, aber auch anspruchsvolle Option für die asymmetrische Synthese dar. Hier beschreiben wir ein neuartiges Konzept einer chemo-enzymatischen Deracemisierung mittels einer Kaskadenreaktion. Die Reakt...

The Michael hydratase - alcohol dehydrogenase (MhyADH) from Alicycliphilus denitrificans was previously identified as a bi-functional enzyme performing a hydration of α,β-unsaturated ketones and subsequent oxidation of the formed alcohols. The investigations of the bi-functionality were based on a spectrophotometric assay and an activity staining i...

The use of water as a nucleophile for Michael additions is still a challenge in organic chemistry. In this report we describe the use of amino acids as catalysts for the Michael addition of water to ,-unsaturated ketones. All 20 proteinogenic amino acids were screened and L-lysine was identified as the best candidate. To obtain a better insight and...

Rhodococcus rhodochrous ATCC 17895 possesses an array of mono- and dioxygenases, as well as hydratases, which makes it an interesting organism for biocatalysis. R. rhodochrous is a Gram-positive aerobic bacterium with a rod-like morphology. Here we describe the features of this organism, together with the complete genome sequence and annotation. Th...

Alkaloids are not only one of the most intensively studied classes of natural products, their wide spectrum of pharmacological activities also makes them indispensable drug ingredients in both traditional and modern medicine. Among the methods for their production, biotechnological approaches are gaining importance, and biocatalysis has emerged as...

A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the di...

Fluorine is commonly applied in pharmaceuticals to block the degradation of bioactive compounds at a specific site of the molecule. Blocking of the reaction center of the enzyme-catalyzed ring closure of 1,2,3,4-tetrahydrobenzylisoquinolines by a fluoro moiety allowed redirecting the berberine bridge enzyme (BBE)-catalyzed transformation of these c...

Berberine bridge enzyme (BBE) catalyses the oxidative formation of an intramolecular C-C bond using (S)-reticuline as the natural substrate to form (S)-scoulerine as the product. To allow application of the enzyme on a preparative scale for the synthesis of novel optically pure berbine and isoquinoline derivatives, an organic solvent is required to...

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natur...

Brücken bauen: Das Berberin-Brücken-Enzym (BBE) wurde für die erste präparative oxidative biokatalytische C-C-Kupplung unter Bildung einer intramolekularen Bindung eingesetzt (siehe Bild). Diese einzigartige Umsetzung benötigt nur O2 als stöchiometrisches Oxidationsmittel und ermöglicht die Synthese von neuartigen enantiomerenreinen (S)-Berbinen 2...

Berberine bridge enzyme (BBE) from the California poppy enantioselectively converts benzylisoquinolines into berbines by oxidative CC coupling that consumes O2 as a stoichiometric oxidant. In their Communication on page 1068 ff., W. Kroutil and co-workers describe the first biocatalytic application of BBE on a preparative scale. Novel optically pur...

Bridging the gap: The berberine bridge enzyme (BBE) was employed for the first preparative oxidative biocatalytic C-C coupling that leads to a new intramolecular bond. This unique transformation requires O2 as sole stoichiometric oxidant and gives access to novel optically pure (S)-berbine 2 and (R)-1-benzyl-1,2,3,4-tetrahydroisoquinoline 1 alkaloi...

Carbon-carbon bond formation is the key transformation in organic synthesis to set up the carbon backbone of organic molecules. However, only a limited number of enzymatic C-C bond forming reactions have been applied in biocatalytic organic synthesis. Recently, further name reactions have been accomplished for the first time employing enzymes on a...

The combination of an oxidation and a reduction in a cascade allows performing transformations in a very economic and efficient fashion. The challenge is how to combine an oxidation with a reduction in one pot, either by running the two reactions simultaneously or in a stepwise fashion without isolation of intermediates. The broader availability of...

A biocatalytic redox-neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L-phenylglycine employing three enzymes. The cascade consisted of three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of d-mandelic acid t...

(Chemical Equation Presented) Quasi-irreversible oxidation of sec-alcohols was achieved via biocatalytic hydrogen transfer reactions using alcohol dehydrogenases employing selected ketones as hydrogen acceptors, which can only be reduced but not oxidized. Thus, only 1 equiv of oxidant was required instead of a large excess. For the oxidation of bot...