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Bioinformatics and Computationally Supported Redesign of Aspartase for β-Alanine Synthesis by Acrylic Acid Hydroamination.
ACS Catal
January 2025
Chemical Biotechnology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, 9747 AG Groningen, the Netherlands.
Aspartate ammonia lyases catalyze the reversible amination of fumarate to l-aspartate. Recent studies demonstrate that the thermostable enzyme from sp. YM55-1 (AspB) can be engineered for the enantioselective production of substituted β-amino acids.
View Article and Find Full Text PDFRedesigning methionine γ-lyase for improved stability and catalytic activity in the β-elimination reaction for the synthesis of thiosulfinates.
Biochimie
January 2025
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, Vavilov street, 32, Moscow, 119991, Russia.
Pyridoxal 5'-phosphate (PLP)-dependent enzymes are involved in many cellular processes and possess unequalled catalytic versatility. Rational design through site-directed mutagenesis is a powerful strategy for creating tailor-made enzymes for a wide range of biocatalytic applications. PLP-dependent methionine γ-lyase (MGL), which degrades sulfur-containing amino acids, is an encouraging enzyme for many therapeutic purposes - from combating bacterial resistant strains and fungi to antitumor activity.
View Article and Find Full Text PDFCytotoxic ROS-Consuming Mn(III) Synzymes: Structural Influence on Their Mechanism of Action.
Int J Mol Sci
December 2024
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124 Parma, Italy.
ROS (i.e., reactive oxygen species) scavenging is a key function of various Mn-based enzymes, including superoxide dismutases (SODs) and catalases, which are actively linked to oxidative stress-related diseases.
View Article and Find Full Text PDFEpigenetic drug screening identifies enzyme inhibitors A-196 and TMP-269 as novel regulators of sprouting angiogenesis.
Sci Rep
January 2025
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Epigenetic therapy has gained interest in treating cardiovascular diseases, but preclinical studies often encounter challenges with cell-type-specific effects or batch-to-batch variation, which have limited identification of novel drug candidates targeting angiogenesis. To address these limitations and improve the reproducibility of epigenetic drug screening, we redesigned a 3D in vitro fibrin bead assay to utilize immortalized human aortic endothelial cells (TeloHAECs) and screened a focused compound library with 105 agents. Compared to the established model using primary human umbilical vein endothelial cells, TeloHAECs needed a higher-density fibrin gel for optimal sprouting, successfully forming sprouts under both normoxic and hypoxic cell culture conditions.
View Article and Find Full Text PDFDe novo biosynthesis of nylon 12 monomer ω-aminododecanoic acid.
Nat Commun
January 2025
Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Nylon 12 is valued for its exceptional properties and diverse industrial applications. Traditional chemical synthesis of nylon 12 faces significant technical challenges and environmental concerns, while bioproduction from plant-extracted decanoic acid (DDA) raises issues related to deforestation and biodiversity loss. Here, we show the development of an engineered Escherichia coli cell factory capable of biosynthesizing the nylon 12 monomer, ω-aminododecanoic acid (ω-AmDDA), from glucose.
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