A5057762796- Enzyme Structure and Function
- Enzyme Catalysis and Immobilization
- Carbohydrate Chemistry and Synthesis
- Microbial Metabolic Engineering and Bioproduction
- Diet, Metabolism, and Disease
- Protein Structure and Dynamics
- Biochemical and biochemical processes
- Plant Gene Expression Analysis
- Enzyme Production and Characterization
- Plant-derived Lignans Synthesis and Bioactivity
- Phytochemicals and Antioxidant Activities
- Glycosylation and Glycoproteins Research
- Metal-Catalyzed Oxygenation Mechanisms
- Plant biochemistry and biosynthesis
- Microbial Metabolites in Food Biotechnology
- X-ray Diffraction in Crystallography
- Natural product bioactivities and synthesis
- Catalytic C–H Functionalization Methods
- Biochemical and Molecular Research
- Crystallization and Solubility Studies
- Amino Acid Enzymes and Metabolism
- Polyamine Metabolism and Applications
- Cyclopropane Reaction Mechanisms
- melanin and skin pigmentation
- Biochemical Acid Research Studies
Graz University of Technology
2019-2025
Austrian Centre of Industrial Biotechnology (Austria)
2023-2025
Health First
2022
University of Graz
2019
Czech Academy of Sciences, Institute of Biotechnology
2017-2019
Abstract Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy‐, epi ‐, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation biocatalytic kinetic resolution corresponding dibenzylbutyrolactones with same 2‐oxoglutarate‐dependent dioxygenase. The reaction can be conducted on 2 g scale, enzyme allows tailoring initial, “natural” structure thus transforms various...
Abstract Biological degradation of natural product glycosides involves, alongside hydrolysis, β-elimination for glycosidic bond cleavage. Here, we discover an O -glycoside β-eliminase (OGE) from Agrobacterium tumefaciens that converts the C3-oxidized -β- d -glucoside phloretin (a plant-derived flavonoid) into aglycone and 2-hydroxy-3-keto-glycal elimination product. While unrelated in sequence, OGE is structurally homologous to, shows effectively same Mn 2+ active site as, C deglycosylating...
The structural motif of hetero-di-C-glycosyl compound is prominent in plant polyphenol natural products and involves two different glycosyl residues (e.g., β-d-glucosyl, β-d-xylosyl) attached to carbons the same phenolic ring. Polyphenol hetero-di-C-glycosides attract attention as specialized ingredients herbal medicines their tailored synthesis by enzymatic C-glycosylation promising overcome limitations low availability expand molecular diversity new-to-nature glycoside structures. However,...
Abstract Glycosylated derivatives of natural product polyphenols display a spectrum biological activities, rendering them critical for both nutritional and pharmacological applications. Their enzymatic synthesis by glycosyltransferases is frequently constrained the limited repertoire characterized enzyme-catalyzed transformations. Here, we explore glycosylation capabilities substrate preferences newly identified plant uridine diphosphate (UDP)-dependent (UGTs) within UGT72 UGT84 families,...
UDP‐glucuronic acid (UDP‐GlcA) is a central precursor in sugar nucleotide biosynthesis and common substrate for C4‐epimerases decarboxylases releasing UDP‐galacturonic (UDP‐GalA) UDP‐pentose products, respectively. Despite the different reactions catalyzed, enzymes are believed to share mechanistic analogy rooted their joint membership short‐chain dehydrogenase/reductase (SDR) protein superfamily: Oxidation at C4 by enzyme‐bound NAD + initiates catalytic pathway. Here, we present...
Abstract Podophyllotoxin ( 1 ) ist einer der bekanntesten Vertreter von natürlich vorkommenden Lignanen. Deoxy‐, epi ‐ und Podophyllotoxin, welche alle Vorstufen für häufig verwendete chemotherapeutische Verbindungen darstellen, wurden mithilfe stereodivergenten Biotransformation biokatalytischen kinetischen Racematspaltung jeweiligen Dibenzylbutyrolactone durch dieselbe 2‐Oxoglutarat‐abhängige Dioxygenase (2‐ODD) hergestellt. Zudem konnte gezeigt werden, dass ein “Upscaling” Reaktion auf 2...
Abstract Understanding enzyme catalysis as connected to protein motions is a major challenge. Here, based on temperature kinetic studies combined with isotope effect measurements, we obtain energetic description of C-H activation in NAD-dependent UDP-glucuronic acid C4 epimerase. Approach from the ensemble-averaged ground state (GS) transition state-like reactive conformation (TSRC) involves, alongside uptake heat ( $${\Delta {{{{{\rm{H}}}}}}}^{{{\ddagger}} }$$ <mml:math...
Polyphenolic aglycones featuring two sugars individually attached via C-glycosidic linkage (di-C-glycosides) represent a rare class of plant natural products with unique physicochemical properties and biological activities. Natural scarcity such di-C-glycosides limits their use-inspired exploration as pharmaceutical ingredients. Here, we show biocatalytic process technology for reaction-intensified production the di-C-β-glucosides representative phenol substrates, phloretin (a flavonoid)...
UDP-glucuronic acid is converted to UDP-galacturonic en route a variety of sugar-containing metabolites. This reaction performed by NAD+-dependent epimerase belonging the short-chain dehydrogenase/reductase family. We present several high-resolution crystal structures from Bacillus cereus. The geometry substrate-NAD+ interactions finely arranged promote hydride transfer. exquisite complementarity between glucuronic and its binding site highlighted observation that unligated cavity occupied...
UDP-glucuronic acid (UDP-GlcA) 4-epimerase illustrates an important problem regarding enzyme catalysis: balancing conformational flexibility with precise positioning. The coordinates the C4-oxidation of substrate by NAD+ and rotation a decarboxylation-prone β-keto intermediate in active site, enabling stereoinverting reduction keto group NADH. We reveal elusive rotational landscape 4-keto intermediate. Distortion sugar ring into boat conformations induces torsional mobility enzyme's binding...
Sugar nucleotide-dependent glycosyltransferases are powerful catalysts of the glycosylation natural products and xenobiotics. The low solubility aglycone substrate often limits synthetic efficiency transformation catalyzed. Here, we explored different approaches solvent engineering for reaction intensification β-glycosylation 15HCM (a C15-hydroxylated, plant detoxification metabolite herbicide cinmethylin) catalyzed by safflower UGT71E5 using UDP-glucose as donor substrate. Use a cosolvent...
The glycosylation of an alcohol group from a sugar nucleotide substrate involves proton release, so the reaction is favored thermodynamically at high pH. Here, we explored expansion alkaline pH range sucrose synthase (SuSy; EC 2.4.1.13) to facilitate enzymatic uridine 5'-diphosphate (UDP)-glucose. apparent equilibrium constant SuSy (UDP-glucose + fructose ↔ UDP) 30 °C increases by ∼4 orders magnitude as raised 5.5 9.0. However, in solution loses ≥80 % its maximum productivity ∼7 when...
UDP‐Glucuronsäure(UDP‐GlcA)‐4‐Epimerase repräsentiert eine wichtige Fragestellung in der Enzymkatalyse: die Balance zwischen konformativer Flexibilität und genauer Positionierung. Das Enzym koordiniert C4‐Oxidation des Substrats durch NAD