Bernd A. Nebel

Bio: Bernd A. Nebel is an academic researcher from University of Stuttgart. The author has contributed to research in topics: Ionic liquid & Catalysis. The author has an hindex of 9, co-authored 18 publications receiving 631 citations.

New Generation of Biocatalysts for Organic Synthesis

Abstract: The use of enzymes as catalysts for the preparation of novel compounds has received steadily increasing attention over the past few years. High demands are placed on the identification of new biocatalysts for organic synthesis. The catalysis of more ambitious reactions reflects the high expectations of this field of research. Enzymes play an increasingly important role as biocatalysts in the synthesis of key intermediates for the pharmaceutical and chemical industry, and new enzymatic technologies and processes have been established. Enzymes are an important part of the spectrum of catalysts available for synthetic chemistry. The advantages and applications of the most recent and attractive biocatalysts--reductases, transaminases, ammonia lyases, epoxide hydrolases, and dehalogenases--will be discussed herein and exemplified by the syntheses of interesting compounds.

Biokatalysatoren für die organische Synthese – die neue Generation

Abstract: Die Verwendung von Enzymen als Katalysatoren zur Synthese neuartiger Verbindungen ist in den letzten Jahren zunehmend in den Fokus geruckt. Entsprechend hohe Erwartungen werden an die Entdeckung und Identifizierung neuer Biokatalysatoren fur die organische Synthese gestellt. Dies spiegelt sich auch in der Komplexitat der adressierten Reaktionen wider. Der Anwendungsbereich von Biokatalysatoren umfasst die Synthese wichtiger Zwischenprodukte fur die pharmazeutische und chemische Industrie sowie die Entwicklung neuer enzymatischer Techniken und Prozesse. Enzyme sind ein wichtiger Teil des Spektrums an Katalysatoren, die der Synthesechemie zur Verfugung stehen. Die Vorteile und Anwendungsmoglichkeiten der neuesten und hochst vielversprechenden Generation von Biokatalysatoren – Reduktasen, Transaminasen, Ammoniak-Lyasen, Epoxidhydrolasen und Dehalogenasen – werden hier vorgestellt und anhand der Synthese von Schlusselmolekulen beispielhaft diskutiert.

Rapid and complete degradation of diclofenac by native soil microorganisms

Abstract: Diclofenac one of the widespread xenobiotics, among other organic micropollutants, is persistent accumulating in different habitats like earth, water, plants and even mammalians. Natural microbial communities in soil and water play a key role in fundamental ecological processes such as regulating the fate of pollution released in the environment. As presented in this study varying concentrations of diclofenac between 0.1 and 1.0 g/L solubilized in a low salt medium could be aerobically degraded by forest soil within less than 10 days. In the course of full degradation, a carboxylated diclofenac intermediate could be isolated and identified by LC-MS/MS-TOF. The carboxylated diclofenac might be a key intermediate to enable a complete biodegradation of diclofenac via 2,6-dichloroaniline and carboxylated 2-hydroxyphenylacetic acid by a microbial consortium.

Role of Biocatalysis in Sustainable Chemistry

Abstract: Based on the principles and metrics of green chemistry and sustainable development, biocatalysis is both a green and sustainable technology. This is largely a result of the spectacular advances in molecular biology and biotechnology achieved in the past two decades. Protein engineering has enabled the optimization of existing enzymes and the invention of entirely new biocatalytic reactions that were previously unknown in Nature. It is now eminently feasible to develop enzymatic transformations to fit predefined parameters, resulting in processes that are truly sustainable by design. This approach has successfully been applied, for example, in the industrial synthesis of active pharmaceutical ingredients. In addition to the use of protein engineering, other aspects of biocatalysis engineering, such as substrate, medium, and reactor engineering, can be utilized to improve the efficiency and cost-effectiveness and, hence, the sustainability of biocatalytic reactions. Furthermore, immobilization of an enzyme ...

2‐Methyltetrahydrofuran (2‐MeTHF): A Biomass‐Derived Solvent with Broad Application in Organic Chemistry

Abstract: 2-Methyl-tetrahydrofuran (2-MeTHF) can be derived from renewable resources (e.g., furfural or levulinic acid) and is a promising alternative solvent in the search for environmentally benign synthesis strategies. Its physical and chemical properties, such as its low miscibility with water, boiling point, remarkable stability compared to other cyclic-based solvents such as THF, and others make it appealing for applications in syntheses involving organometallics, organocatalysis, and biotransformations or for processing lignocellulosic materials. Interestingly, a significant number of industries have also started to assess 2-MeTHF in several synthetic procedures, often with excellent results and prospects. Likewise, preliminary toxicology assessments suggest that the use of 2-MeTHF might even be extended to more processes in pharmaceutical chemistry. This Minireview describes the properties of 2-MeTHF, the state-of-the-art of its use in synthesis, and covers several outstanding examples of its application from both industry and academia.

Nature's chemical signatures in human olfaction: a foodborne perspective for future biotechnology.

Abstract: The biocatalytic production of flavor naturals that determine chemosensory percepts of foods and beverages is an ever challenging target for academic and industrial research. Advances in chemical trace analysis and post-genomic progress at the chemistry-biology interface revealed odor qualities of nature's chemosensory entities to be defined by odorant-induced olfactory receptor activity patterns. Beyond traditional views, this review and meta-analysis now shows characteristic ratios of only about 3 to 40 genuine key odorants for each food, from a group of about 230 out of circa 10 000 food volatiles. This suggests the foodborn stimulus space has co-evolved with, and roughly match our circa 400 olfactory receptors as best natural agonists. This perspective gives insight into nature's chemical signatures of smell, provides the chemical odor codes of more than 220 food samples, and beyond addresses industrial implications for producing recombinants that fully reconstruct the natural odor signatures for use in flavors and fragrances, fully immersive interactive virtual environments, or humanoid bioelectronic noses.

Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently

Abstract: The amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the ‘search space’ of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (Kd) and catalytic (kcat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving kcat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the ‘best’ amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole, simultaneously, this offers opportunities for protein improvement not readily available to natural evolution on rapid timescales. Intelligent landscape navigation, informed by sequence-activity relationships and coupled to the emerging methods of synthetic biology, offers scope for the development of novel biocatalysts that are both highly active and robust.