Uwe T Bornscheuer

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Verified

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• Prof. Dr.
• Head of Department at Universität Greifswald

Staphylococcus aureus is a versatile pathogen, renowned for its arsenal of virulence and immune evasion factors. Several S. aureus virulence factors have been targeted in vaccination trials; however, so far, without success. Promising new vaccine candidates are the staphylococcal serine protease-like proteins (Spl A–F), which are involved in the pa...

The expression of recombinant proteins in heterologous hosts is a common strategy to obtain larger quantities of the "protein of interest" (POI) for scientific, therapeutic or commercial purposes. However, the experimental success of such an approach critically depends on the choice of an appropriate host system to obtain biologically active forms...

Enzymatic depolymerization of polyethylene terephthalate (PET) towards monomer recycling offers a green route to a circular plastic economy, with scale-up currently underway. Yet, inconsistent assessment methods hinder clear comparisons between various PET hydrolases. This Perspective aims to identify critical gaps in this dynamic research field an...

Supported by rapid technological advancements, biocatalytic applications have matured into sustainable, scalable, and cost‐competitive alternatives to established chemical catalysis. This review presents the most recent examples of enzyme‐based solutions for the manufacturing of molecules with extended carbon–carbon frameworks and multiple stereoge...

Ultrahigh-throughput methods such as flow cytometry are ideal tools for the directed evolution of enzymes by enabling the screening of up to 10⁹ variants per day. In this study, we developed an assay based on fluorescence-activated cell sorting (FACS) for the detection and engineering of amidase activity in whole cells. The assay establishes a stab...

Kurzzusammenfassung Unterstützt durch rasche technologische Fortschritte haben sich biokatalytische Anwendungen zu einer nachhaltigen, skalierbaren und kostengünstigen Alternative zur etablierten chemischen Katalyse entwickelt. In dieser Arbeit werden die neuesten Beispiele für enzymbasierte Ansätze zur Herstellung von Molekülen mit komplexen Kohle...

Carbohydrate‐active enzymes (CAZymes) are critical for sustainable biomass utilization due to their ability to degrade complex polysaccharides. Frequently, a multimodularity can be observed combining several CAZyme domains and activities in close proximity which can benefit this degradation process. In this study, three multimodular xylanolytic car...

Pharmaceuticals and bioactive molecules often contain chiral pyrrolidines and azepanes as key structural elements. Traditional synthesis methods involve expensive catalysts and multiple steps. More efficient, selective, and environmentally friendlier synthetic routes are needed to improve accessibility to these valuable building blocks. This study...

The supply of blood products such as red blood cells poses a challenge due to rising demand and declining donor numbers. Careful matching of blood products of different types is required. Only type O of the blood types A, B, AB and O can be received by any patient without transfusion incompatibilities. Therefore, O‐type blood can be considered “uni...

The methylation of small molecules is of immense value to various chemical industries. Since chemical alkylation requires rather unselective and harsh reaction conditions, sustainable biocatalytic approaches are highly desired. Methyltransferases, particularly N‐methyltransferases (NMTs), facilitate the selective introduction of methyl (and other a...

Staphylococcus aureus is a Gram-positive opportunistic pathogen that has colonized nearly 30% of the human population and can cause life-threatening infections. S. aureus exports a variety of virulence factors, such as a novel set of extracellular serine protease-like proteins (Spls). Spls are expressed by most clinical isolates of S. aureus, but t...

Acute pancreatitis (AP) is characterised by self-digestion of the pancreas by its own proteases. This pathophysiological initiating event in AP occurs inside pancreatic acinar cells where intrapancreatic trypsinogen becomes prematurely activated by cathepsin B (CTSB), and induces the digestive protease cascade, while cathepsin L (CTSL) degrades try...

Plastics (synthetic polymers) play an essential role in modern living, but their uncontrolled disposal has led to severe environmental impacts. The production of plastics is based on fossil feedstocks, which are associated with detrimental climate effects. Thus, sustainable concepts for the re- and upcycling of plastic waste are urgently required....

Polyurethane (PUR), the fifth most prevalent synthetic polymer, substantially contributes to the global plastic waste problem. Biotechnology‐based recycling methods have recently emerged as innovative solutions to plastic waste disposal and sparked interest among scientific communities and industrial stakeholders in discovering and designing highly...

As global plastic consumption and littering escalate, innovative approaches to sustainable waste management are crucial. Enzymatic depolymerization has emerged as a promising recycling method for polyesters via monomer recovery under mild conditions. However, current research mainly focuses on using a single plastic feedstock, which can only be der...

Chiral heterocyclic alcohols and amines are frequently used building blocks in the synthesis of fine chemicals and pharmaceuticals. Herein, we report a one-pot photoenzymatic synthesis route for N-Boc-3-amino/hydroxy-pyrrolidine and N-Boc-4-amino/hydroxy-azepane with up to 90% conversions and >99% enantiomeric excess. The transformation combines a...

Biocatalysis provides an eco-friendly and efficient method for the synthesis of fine chemicals, pharmaceuticals, and biofuels. However, the catalytic performance of enzymes is greatly reduced when they react under non-optimal...

Global plastic production exceeded 400 million tons in 2022, urgently demanding improved waste management and recycling strategies for a circular plastic economy. While the enzymatic hydrolysis of polyethylene terephthalate (PET) has become feasible on industrial scales, efficient enzymes targeting other hydrolyzable plastic types, such as polyuret...

Cysteine cathepsins such as cathepsin B and L play an important role in numerous diseases like acute pancreatitis or SARS-CoV-2 and therefore have high potential for the development of new therapeutics. To be able to screen for potent and selective inhibitors sufficient amounts of protein are required. Here, we present an easy and efficient protoco...

In this study, a selective C−H‐oxyfunctionalization using an unspecific peroxygenase (UPO) enabled an efficient biosynthetic route for the synthesis of grevillic acid (GA), a natural antioxidant. The route commenced with the release of o‐coumaric acid (oCA) from trans‐2‐coumaric acid glucoside (trans‐CAG) using commercially available β‐glucosidase...

The ability to predict and design protein structures has led to numerous applications in medicine, diagnostics and sustainable chemical manufacture. In addition, the wealth of predicted protein structures has advanced our understanding of how life's molecules function and interact. Honouring the work that has fundamentally changed the way scientist...

Global plastic production exceeded 400 million tons in 2022, urgently demanding improved waste management and recycling strategies for a circular plastic economy. While the enzymatic hydrolysis of polyethylene terephthalate (PET) has become feasible on industrial scales, efficient enzymes targeting other hydrolysable plastic types such as polyureth...

The ability to predict and design protein structures has led to numerous applications in medicine, diagnostics and sustainable chemical manufacture. In addition, the wealth of predicted protein structures advances our understanding about how life’s molecules function and interact. Honouring the work that has fundamentally changed the way scientists...

Poly(ethylene furanoate) (PEF) is considered the greener alternative to poly(ethylene terephthalate) (PET) and other plastics, as it can be produced 100% biobased from renewable resources based on the building blocks 2,5-furandicarboxylic acid (FDCA) and ethylene glycol (EG). So far, most of the literature has dealt with the synthesis and detailed...

Over the past years, enzymatic depolymerization of PET, one of the most widely used plastics worldwide, has become very efficient leading to the end products terephthalic acid (TPA) and ethylene glycol (EG) used for PET re‐synthesis. Potent alternatives to these monomers are the intermediates BHET and MHET, the mono‐ and di‐esters of TPA and EG whi...

An integrated system of three membrane bioreactors (MBRs) has been developed that cascades three different enzymatic reactions. The integrated system was applied to produce hydroxytyrosol acetate from oleuropein extracted from olive leaves. Different reactor configurations for each reaction were tested and individually optimized to select the MBR t...

A concept of combining photocatalytically generated hydrogen with green enzymatic reductions is demonstrated. The developed photocatalytic formic acid (FA) dehydrogenation setup based on Pt(x)@TiO2 shows stable hydrogen generation activity, which is two orders of magnitude higher than reported values of state‐of‐the‐art systems. Mechanistic studies...

Esters are valuable aroma compounds and can be produced enzymatically by Baeyer‐Villiger monooxygenases (BVMOs) from (aliphatic) ketone precursors. However, a genetically encoded biosensor system for the assessment of BVMO activity and the detection of reaction products is missing. In this work, we assembled a synthetic enzyme cascade – featuring a...

Aromatic monomers obtained by selective depolymerization of the lignin β‐O‐4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one‐pot catalytic lignin β‐O‐4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side‐chains. This cascade cons...

Polyethylene (PE) is the most commonly used plastic type in the world, contributing significantly to the plastic waste crisis. Microbial degradation of PE in natural environments is unlikely due to its inert saturated carbon‐carbon backbones, which are difficult to break down by enzymes, challenging the development of a biocatalytic recycling metho...

Branched aromatic α-amino acids are valuable building blocks in natural products and pharmaceutically active compounds. However, their chemical or enzymatic synthesis is challenging due to the presence of two stereocenters. We design phenylalanine ammonia lyases (PAL) variants for the direct asymmetric synthesis of β-branched aromatic α-amino acids...

Plastic-degrading enzymes facilitate the biocatalytic recycling of poly(ethylene terephthalate) (PET), a significant synthetic polymer, and substantial progress has been made in utilizing PET hydrolases for industrial applications. To fully exploit the potential of these enzymes, a deeper mechanistic understanding followed by targeted protein engin...

Polyethylene (PE) is the most commonly used plastic type in the world, contributing significantly to the plastic waste crisis. Microbial degradation of PE in natural environments is unlikely due to its inert saturated carbon‐carbon backbones, which are difficult to break down by enzymes, challenging the development of a biocatalytic recycling metho...

Darwinian evolution has given rise to all the enzymes that enable life on Earth. Mimicking natural selection, scientists have learned to tailor these biocatalysts through recursive cycles of mutation, selection and amplification, often relying on screening large protein libraries to productively modulate the complex interplay between protein struct...

SusC/D-like proteins are essential components of glycan utilization machineries in Bacteroidota , but remain unknown in other bacterial phyla. The glycan-binding SusD-like protein forms a ‘lid’ on top of the SusC-like TonB-dependent transporter (TBDT) and both are structurally designed to function as a complex in sugar uptake. In comparison, Gammap...

While plastics like polyethylene terephthalate can already be degraded efficiently by the activity of hydrolases, other synthetic polymers like polyurethanes (PUs) and polyamides (PAs) largely resist biodegradation. In this study, we solved the first crystal structure of the metagenomic urethanase UMG‐SP‐1, identified highly flexible loop regions t...

The demand for the reduced nicotinamide adenine dinucleotide (1,4-NADH) and reduced nicotinamide adenine dinucleotide phosphate 1,4-NAD(P)H in industrial processes, particularly in the pharmaceutical sector, necessitates their continuous regeneration to mitigate cost implications [1]. In this respect, direct electrochemical cofactor regeneration is...

Aromatic monomers obtained by selective depolymerization of the lignin β‐O‐4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one‐pot catalytic lignin β‐O‐4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side‐chains. This cascade cons...

The AMP-forming acetyl-CoA synthetase is regulated by lysine acetylation both in bacteria and eukaryotes. However, the underlying mechanism is poorly understood. The Bacillus subtilis acetyltransferase AcuA and the AMP-forming acetyl-CoA synthetase AcsA form an AcuA•AcsA complex, dissociating upon lysine acetylation of AcsA by AcuA. Crystal structu...

Biocatalysis is a rapidly evolving field with increasing impact in organic synthesis, chemical manufacturing and medicine. The Faraday Discussion reflected the current state of biocatalysis, covering the design of de novo enzymatic activities, but especially methods for the improvement of enzymes targeting a broad range of applications (i.e., hydro...

While plastics like polyethylene terephthalate can already be degraded efficiently by the activity of hydrolases, other synthetic polymers like polyurethanes (PUs) and polyamides (PAs) largely resist biodegradation. In this study, we solved the first crystal structure of the metagenomic urethanase UMG‐SP‐1, identified highly flexible loop regions t...

This article presents an overview of the evolution, impact, and challenges of plastics, focusing on the difficulties in recycling processes and introducing biocatalytic technologies as a promising solution for efficient plastic degradation. While there are many obstacles in accessability of plastics for enzymatic degradation, recent achievements in...

In the last decades, biocatalysis has offered new perspectives for the synthesis of (chiral) amines, which are essential building blocks for pharmaceuticals, fine and bulk chemicals. In this regard, amidases have been employed due to their broad substrate scope and their independence from expensive cofactors. To expand the repertoire of amidases, t...

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of car...

Carboxylic ester hydrolases with the capacity to degrade polyesters are currently highly sought after for their potential use in the biological degradation of PET and other chemically synthesized polymers. Here, we describe MarCE, a carboxylesterase family protein identified via genome mining of a Maribacter sp. isolate from the marine sponge Stell...

Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via increased zooplankton grazing and viral lysis. While bacterial consumption of algal biomass during blooms is well-studied, little is known about the concurrent recycling of these substantial amounts of bacterial necromass. We demonstrate t...

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of car...

The co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two d...

Plastic-degrading enzymes hold promise for biocatalytic recycling of poly(ethylene terephthalate) (PET), a key synthetic polymer. Despite their potential, the current activity of PET hydrolases is not sufficient for industrial use. To unlock their full potential, a deep mechanistic understanding followed by protein engineering is required. Using cu...

The direct electrochemical reduction of nicotinamide adenine dinucleotide (NAD⁺) results in various products, complicating the regeneration of the crucial 1,4‐NADH cofactor for enzymatic reactions. Previous research primarily focused on steady–state polarization to examine potential impacts on product selectivity. However, this study explores the i...

This chapter describes the strategies for the optimization of enzymes for industrial applications using protein engineering methods. Firstly, the two main concepts—rational protein design and directed evolution—are introduced and the major differences are explained. Molecular biology methods for generating mutant libraries by site-directed mutagene...

Hydroxycinnamic acid amides are believed to have antioxidant, antidiabetic, cytotoxic, anticancer, neuroprotective, and antiinflammatory properties, making them interesting target molecules for potential applications in the food, cosmetics, and pharmaceutical industries. Here, we describe the synthesis of hydroxycinnamic acid amides starting from h...

Aromatic ammonia lyases (AALs) and tyrosine/phenylalanine ammonia mutases (TAM/PAM) are 3,5‐dihydro‐5‐methylidene‐4H‐imidazol‐4‐one (MIO)‐dependent enzymes. Usually, the MIO moiety is autocatalytically formed from the tripeptide Ala‐Ser‐Gly (ASG) and acts as an electrophile during the enzymatic reaction. However, the MIO‐forming residues (ASG) have...

Novel concepts to utilize carbon dioxide are required to reach a circular carbon economy and minimize environmental issues. To achieve these goals, photo‐, electro‐, thermal‐, and biocatalysis are key tools to realize this, preferentially in aqueous solutions. Nevertheless, catalytic systems that operate efficiently in water are scarce. Here, we pr...

The demand for the reduced nicotinamide adenine dinucleotide (1,4-NADH) and reduced nicotinamide adenine dinucleotide phosphate 1,4-NAD(P)H in industrial processes, particularly in the pharmaceutical sector, necessitates their continuous regeneration to mitigate cost implications [1]. In this respect, direct electrochemical cofactor regeneration is...

Novel concepts to utilize carbon dioxide are required to reach a circular carbon economy and minimize environmental issues. To achieve these goals, photo‐, electro‐, thermal‐, and biocatalysis are key tools to realize this, preferentially in aqueous solutions. Nevertheless, catalytic systems that operate efficiently in water are scarce. Here, we pr...

Production of commodity chemicals, such as benzene, toluene, ethylbenzene, and xylenes (BTEX), from renewable resources is key for a sustainable society. Biocatalysis enables one‐pot multistep transformation of bioresources under mild conditions, yet it is often limited to biochemicals. Herein, we developed a non‐natural three‐enzyme cascade for on...

Protein engineering is essential for altering the substrate scope, catalytic activity and selectivity of enzymes for applications in biocatalysis. However, traditional approaches, such as directed evolution and rational design, encounter the challenge in dealing with the experimental screening process of a large protein mutation space. Machine lear...

Biocatalysis harnesses enzymes to make valuable products. This green technology is used in countless applications from bench scale to industrial production and allows practitioners to access complex organic molecules, often with fewer synthetic steps and reduced waste. The last decade has seen an explosion in the development of experimental and com...

Biotechnological recycling offers a promising solution to address the environmental concerns associated with waste plastics, particularly polyethylene terephthalate (PET), widely utilized in packaging materials and textiles. To advance the development of a bio‐based circular plastic economy, innovative upcycling strategies capable of generating hig...

Biotechnologisches Recycling bietet eine vielversprechende Lösung für die Umweltprobleme im Zusammenhang mit Kunststoffabfällen, insbesondere für Polyethylenterephthalat (PET), das häufig in Verpackungsmaterialien und Textilien verwendet wird. Um die Entwicklung einer biobasierten Kreislaufwirtschaft für Kunststoffe voranzutreiben, sind innovative...

Enzyme‐catalyzed late‐stage functionalization (LSF), such as methylation of drug molecules and lead structures, enables direct access to more potent active pharmaceutical ingredients (API). S‐adenosyl‐l‐methionine‐dependent methyltransferases (MTs) can play a key role in the development of new APIs, as they catalyze the chemo‐ and regioselective me...

Die Herstellung von chemischen Grundstoffen wie Benzol, Toluol, Ethylbenzol und Xylol (BTEX) aus erneuerbaren Ressourcen ist der Schlüssel zu einer nachhaltigen Gesellschaft. Die Biokatalyse ermöglicht die Ein-Topf-Mehrschritt-Transformation von Bioressourcen unter milden Bedingungen, ist jedoch oft auf Biochemikalien beschränkt. Wir haben eine nic...

Enzyme‐catalyzed late‐stage functionalization (LSF), such as methylation of drug molecules and lead structures, enables direct access to more potent active pharmaceutical ingredients (API). S‑adenosyl‐l‐methionine‐dependent methyltransferases (MTs) can play a key role in the development of new APIs, as they catalyze the chemo‐ and regioselective me...

Endo-1,4-β-xylanases belonging to the glycoside hydrolase (GH) 11 family hydrolyze the β-1,4-glycosidic linkages in the xylan backbone to convert polymeric xylan into xylooligosaccharides. GH11 xylanases play an essential role in sugar metabolism and are one of the most widely used enzymes in various industries, such as pulp and paper, food and fee...