Simon Waltzer

Bio: Simon Waltzer is an academic researcher from University of Freiburg. The author has contributed to research in topics: Hydrolase & Biocatalysis. The author has an hindex of 8, co-authored 11 publications receiving 151 citations.

Regio- and Stereoselective Aliphatic-Aromatic Cross-Benzoin Reaction: Enzymatic Divergent Catalysis.

Abstract: The catalytic asymmetric synthesis of chiral 2-hydroxy ketones by using different thiamine diphosphate dependent enzymes, namely benzaldehyde lyase from Pseudomonas fluorescens (PfBAL), a variant of benzoylformate decarboxylase from Pseudomonas putida (PpBFD-L461A), branched-chain 2-keto acid decarboxylase from Lactococcus lactis (LlKdcA) and a variant of pyruvate decarboxylase from Acetobacter pasteurianus (ApPDC-E469G), was studied. Starting with the same set of substrates, substituted benzaldehydes in combination with different aliphatic aldehydes, PfBAL and PpBFD-L461A selectively deliver the (R)- and (S)-2-hydroxy-propiophenone derivatives, respectively. The (R)- and (S)-phenylacetylcarbinol (1-hydroxy-1-phenylacetone) derivatives are accessible in a similar way using LlKdcA and ApPDC-E469G, respectively. In many cases excellent stereochemical purities (>98 % enantiomeric excess) could be achieved. Hence, the regio- and stereochemistry of the product in the asymmetric aliphatic–aromatic cross-benzoin reaction can be controlled solely by choice of the appropriate enzyme or enzyme variant.

Tailoring the S‐Selectivity of 2‐Succinyl‐5‐enolpyruvyl‐6‐hydroxy‐3‐cyclohexene‐1‐carboxylate Synthase (MenD) from Escherichia coli

Abstract: The thiamine diphosphate (ThDP)-dependent enzyme 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase from Escherichia coli (EcMenD, E.C. 2.2.1.9) catalyzes the carboligation of α-ketoglutarate (α-KG) and various benzaldehyde derivatives with excellent chemo- as well as high R-selectivity (enantiomeric excess (ee) >93 %) to yield chiral α-hydroxy ketones. Based on the recently developed S-pocket concept, we engineered S-selective EcMenD variants by optimizing the steric properties and stabilization of the acceptor substrate in the S-pocket. Moreover, the moderate S-selectivity of the EcMenD variant I474A/F475G described recently for the carboligation of α-KG and benzaldehyde (ee=75 %) could be improved by selective destabilization of the R-pathway, which resulted in the variant I474A/F475G/R395Y (ee=85 % S). Subsequent investigation of the acceptor substrate range of this new variant revealed high S-selectivity especially with meta-substituted benzaldehydes, which gave access to 5-hydroxy-4-oxo-5-arylpentanoates with excellent enantioselectivities of up to 99 % ee S. Thus, opening the S-pocket and simultaneous destabilization of the R-pathway provides a potential general new strategy to enhance the S-selectivity of ThDP-dependent enzymes.

Phd by thesis

Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Engineering new catalytic activities in enzymes

Abstract: The efficiency, selectivity and sustainability benefits offered by enzymes are enticing chemists to consider biocatalytic transformations to complement or even supplant more traditional synthetic routes. Increasing demands for efficient and versatile synthetic methods, combined with powerful new discovery and engineering tools, has prompted innovations in biocatalysis, especially the development of new enzymes for precise transformations or ‘molecular editing’. As a result, the past decade has witnessed an impressive expansion of the catalytic repertoire of enzymes to include new and useful transformations not known (or relevant) in the biological world. In this Review we illustrate various ways in which researchers have approached using the catalytic machineries of enzymes for new-to-nature transformations. These efforts have identified genetically encoded catalysts that can be tuned and diversified by engineering the protein sequence, particularly by directed evolution. Discovery and improvement of these new enzyme activities is opening a floodgate that connects the chemistry of the biological world to that invented by humans over the past 100 years. Advances in enzyme performance and capabilities are making them increasingly attractive to synthetic chemists. In this Review Chen and Arnold outline the ways that enzymes have been engineered to achieve reactivities well beyond their original functions.

Enantioselective Chemo- and Biocatalysis: Partners in Retrosynthesis.

Abstract: Recent developments of stereoselective biocatalytic and chemocatalytic methods are discussed. The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focused attention on retrosynthetic considerations and analysis. The transformations presented are organized according to bond disconnections and attendant synthetic methods. The review is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches. It depicts for researchers in bio- and chemocatalysis a road map of challenges and opportunities for the evolution (and at times revolution) in chemical synthesis.

Design and Evolution of Enzymes for Non-natural Chemistry

Abstract: Enzymes are used in biocatalytic processes for the efficient and sustainable production of pharmaceuticals, fragrances, fine chemicals, and other products. Most bioprocesses exploit chemistry found in nature, but we are now entering a realm of biocatalysis that goes well beyond. Enzymes have been engineered to catalyze reactions previously only accessible with synthetic catalysts. Because they can be tuned by directed evolution, many of these new biocatalysts have been shown to perform abiological reactions with high activity and selectivity. We discuss recent examples, showcase catalyst improvements achieved using directed evolution, and comment on some current and future implications of non-natural enzyme evolution for sustainable chemical synthesis.

Building Bridges: Biocatalytic C-C-Bond Formation toward Multifunctional Products.

Abstract: Carbon-carbon bond formation is the key reaction for organic synthesis to construct the carbon framework of organic molecules. The review gives a selection of biocatalytic C-C-bond-forming reactions which have been investigated during the last 5 years and which have already been proven to be applicable for organic synthesis. In most cases, the reactions lead to products functionalized at the site of C-C-bond formation (e.g., α-hydroxy ketones, aminoalcohols, diols, 1,4-diketones, etc.) or allow to decorate aromatic and heteroaromatic molecules. Furthermore, examples for cyclization of (non)natural precursors leading to saturated carbocycles are given as well as the stereoselective cyclopropanation of olefins affording cyclopropanes. Although many tools are already available, recent research also makes it clear that nature provides an even broader set of enzymes to perform specific C-C coupling reactions. The possibilities are without limit; however, a big library of variants for different types of reactions is required to have the specific enzyme for a desired specific (stereoselective) reaction at hand.