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Andreas Liese

Publications and source records attributed to Andreas Liese.

11 recordsLinked to original sources
PubMed2006

Overcoming the thermodynamic limitation in asymmetric hydrogen transfer reactions catalyzed by whole cells.

Whole lyophilized cells of an Escherichia coli overexpressing the alcohol dehydrogenase (ADH-'A') from Rhodococcus ruber DSM 44541 were used for the asymmetric reduction of ketones to secondary alcohols. The recycling of the required nicotinamide cofactor (NADH) was achieved in a coupled-substrate process. In the course of the reaction the ketone is reduced to the alcohol and the hydrogen donor 2-propanol is oxidized to acetone by one enzyme. This leads to a thermodynamic equilibrium between all four components determining the maximum achievable conversion. To overcome this limitation an in situ product removal technique (ISPR) for the application with whole cells was developed. In this method the most volatile compound is separated from the reaction vessel by an air flow resulting in a shift of the equilibrium towards the desired secondary alcohol. The so-called stripping process represents a simple and efficient method to overcome the thermodynamic limitation in biocatalytic reactions. Employing this method, the conversion of selected biotransformations was increased up to completeness.

Alcohol Dehydrogenase↗
PubMed2006

Continuous homogeneous asymmetric transfer hydrogenation of ketones: lessons from kinetics.

Is polymer enlargement of homogeneous catalysts a tedious task? Is not batch operation with homogeneous catalysts the optimum performance point for homogeneous catalysis? Is kinetic modelling relevant to more than academic questions in homogeneous catalysis? Can all answers for a given system be answered satisfactory? In the authors' view, answers to these questions are no, no, yes, and depends. Polymer enlargement allowed the continuous operation of transfer hydrogenation in a chemical membrane reactor with total turnover numbers of up to 2.6 x 10(3) and a space-time yield of 0.58 kg L(-1) d(-1) with an enantiomeric ratio of 26.8 (enantiomeric excess 92.8 %) for a conversion level of 80 %. This was predicted from simulation conducted with a model from kinetic batch experiments adopted for continuous application. These simulations for the polymer-enlarged and the unmodified catalyst show that achieving comparable performance cannot be obtained by batch operation.

Alcohols↗
PubMed2005

Technical application of biological principles in asymmetric catalysis.

The production of enantiopure compounds is becoming increasingly important to the chemical and biotechnological industries. Bioorganic transformations look set to meet this demand due to their inherently regio- and stereoselective natures. In this sense, biosynthesis needs to be viewed as "chemistry by nature". Biological principles that have been optimized over thousands of years experience a new renaissance when used for technical asymmetric catalysis; however, to be able to use them, we need an appropriate technology: reaction engineering. Indeed, various biological principles are already being applied in technical asymmetric synthesis without the scientific community at large being aware of this.

Biology↗
PubMed2004

Biotechnological applications of hydrogenases.

Hydrogenases have found use in a variety of biotechnological applications, including biohydrogen production, wastewater treatment, the prevention of microbial-induced corrosion and the generation and regeneration of NADP cofactors. In the future, advances in genome mining and screening techniques are likely to identify new hydrogenases for novel applications.

Bacteria↗
PubMed2003

Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 8. Pharmacological optimization of orally bioavailable 2-pyridone-containing peptidomimetics.

The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P(2) substituent present in the peptidomimetic portion of the inhibitors. The pharmacokinetics of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an alpha,beta-unsaturated ethyl ester fragment and either an ethyl or propargyl P(2) moiety displayed the most promising combination of 3C enzyme inhibition (k(obs)/[I] 170 000-223 000 M(-1) s(-1)), antiviral activity (EC(50) = 0.047-0.058 microM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 microM; 7 h CM-monkey plasma levels = 0.057-0.896 microM).

3C Viral Proteases↗
PubMed2002

Optimization of the enzymatic synthesis of O-glycan core 2 structure by use of a genetic algorithm.

The enzymatic synthesis of Gal-beta 1,3[GlcNAc-beta 1,6]-GalNAc-alpha 1-OBn (core 2-Bn) using a multi-enzyme system consisting of a beta-galactosidase (EC 3.2.1.23) from bovine testes and a recombinant core 2 beta 1,6-GlcNAc transferase (C2GnT, EC 2.4.1.102) was empirically optimized by the use of a genetic algorithm. After variation of seven relevant parameters and performance of 56 experiments, two local maxima regarding the selection criteria could be found after four generations of optimization. The selectivity of core 2-Bn formation showed values up to 90%.

Algorithms↗
PubMed2002

Genetic algorithms as a tool for capillary electrophoresis method development.

Capillary electrophoresis is a powerful and versatile analytical tool due to the wide range of separation variables and separation methods possible. CE permits the combination of multiple separation mechanisms (e.g., chiral modifiers, polarity, pH) for the analysis of a large variety of compounds. The main advantage of CE (i.e., the broad range of separation variables) has thus far limited its application. This is due to the nonlinear influence and interactions of different parameters on separation quality, making it difficult to predict trends for the optimization of separation systems and hence hindering CE method development. In this paper, we present a means for rationalizing method development for CE separations using a genetic algorithm. We provide selected examples of separation enhancements achieved in the field of nucleotide and nucleotide sugar separation. An improved method for the enantioselective separation of amino acid derivatives (2-acetylamino-3-phenyl-propionic acid) will also be presented.

Adenine Nucleotides↗
PubMedDate not supplied

The utilization of renewable resources in German industrial production.

Renewable resources will be an increasingly important issue for the chemical industry in the future. In the context of white biotechnology, they represent the intersection point of agriculture and the chemical industry. The scarcity and related increase in the price of fossil resources make renewable resources an interesting alternative. If one considers the production of bulk chemicals, it is evident that for this area besides the C sources, sugar and starch, new sources of raw materials must be opened up. One possible solution is to utilize lignocellulose both for materials and energy. This article discusses this interesting prospective for the future, particularly from the point of view of the German industry.

Biotechnology↗