hPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders.

Astrocytes, the most abundant glial cell type in the brain, play crucial roles in maintaining homeostasis within the central nervous system (CNS). Impairment or abnormalities of typical astrocyte functions in the CNS serve as a causative or contributing factor in numerous neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Currently, disease-modeling and drug-screening approaches, primarily focused on human astrocytes, rely on human pluripotent stem cell (hPSC)-derived astrocytes.

Activation of thiamine diphosphate in pyruvate decarboxylase from Zymomonas mobilis.

Replacement of tryptophan 392 located in the active site cavity of pyruvate decarboxylase (PDC; EC 4.1.1.

Active site mutants of pyruvate decarboxylase from Zymomonas mobilis--a site-directed mutagenesis study of L112, I472, I476, E473, and N482.

The homotetrameric pyruvate decarboxylase (PDC) from Zymomonas mobilis requires the cofactors thiamin diphosphate and Mg2+ for catalytic activity. We have investigated the role of various amino acid residues in the direct environment of the active site. The role of residue E473 in the catalytic activity and stability of the enzyme was probed by several mutations.

Application of alpha-keto acid decarboxylases in biotransformations.

The advantages of using enzymes in the synthesis of organic compounds relate to their versatility, high reaction rates, and regio- and stereospecificity and the relatively mild reaction conditions involved. Stereospecificity is especially important in the synthesis of bioactive molecules, as only one of the enantiomeric forms usually manifests bioactivity, whereas the other is often toxic. Although enzymes which catalyze asymmetric carbon-carbon bond formation are of great importance in bioorganic chemistry, only a few examples are known for thiamin diphosphate (ThDP)-dependent enzymes, whereas transformations using e.