Formation of Aliphatic and Aromatic α-Hydroxy Ketones by Zygosaccharomyces bisporus

The wild-type yeast strain Zygosaccharomyces bisporus CBS 702 produced a-hydroxy-ketones (acyloins) from amino acid precursors after transamination to the corresponding 2-oxo acids. The key enzyme of the subsequent decarboxylation and C-C bond forming reaction, pyruvate decarboxylase (PDC), was examined for its substrate- and stereo-specific-ity. A wide variety of saturated and unsaturated aliphatic and aromatic aldehydes was successfully converted to acyloins. 19 of the biotransformation products identified had not been reported as natural substances before. Product yields were strongly affected by substrate structure. © 2000, Verlag der Zeitschrift für Naturforschung. All rights reserved

Purification, characterisation and cDNA sequencing of pyruvate decarboxylase from Zygosaccharomyces bisporus

Cells of the wild-type yeast strain Zygosaccharomyces bisporus CBS 702 form alpha-hydroxy ketones from aromatic amino acid precursors during fermentation, Pyruvate decarboxylase (PDC, E.C. 4.1.1.1), the key enzyme of this biotransformation catalysing the nonoxidative decarboxylation of pyruvate and other 2-oxo-acids, was purified and characterised. The active enzyme is homotetrameric (alpha(4)) with a molecular mass of about 244 kDa, Activation of PDC by its substrate pyruvate results in a sigmoidal dependence of the reaction rate from substrate concentration (apparent K-m value 1.73 mM; Hill coefficient 2.10). A cDNA library was screened using a PCR-based procedure, and a 1856 bp cDNA of PDC was identified and sequenced. The cDNA encodes a polypeptide of 563 amino acid residues (monomeric unit), Sequence alignments demonstrate high homologies (> 80%) to PDC genes from Saccharomyces cerevisiae, Kluyveromyces lactis and Kluyveromyces marxianus.DF

Enzymatische Bildung aromaaktiver [alpha]-Hydroxyketone mit der Wildhefe Zygosaccharomyces bisporus

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A GATA3-specific DNAzyme attenuates sputum eosinophilia in eosinophilic COPD patients: A feasibility randomized clinical trial

BACKGROUND: A subset of COPD-patients presents with eosinophilic airway inflammation. While treatment of asthmatic patients with the GATA3-specific DNAzyme SB010 attenuated sputum eosinophilia after allergen challenge, this specific treatment has not been evaluated in patients with COPD. Our objective was to evaluate the feasibility and safety of inhaled SB010 in COPD patients with sputum eosinophilia. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicentre clinical trial in COPD-patients with sputum eosinophilia (>/=2.5% non-squamous cells). Patients inhaled 10 mg SB010 bid or matching placebo via the controlled inhalation system AKITA2 APIXNEB for 28 days. Endpoints included the feasibility of the study (primary), patient's safety, sputum eosinophils, FENO, lung function, symptoms, and biomarkers. The study was registered in the German Clinical Trials Register: DRKS00006087. RESULTS: One hundred thirty patients were screened, 23 patients were randomized (FEV1 49.4 +/- 11.5%; sputum eosinophils 8.0 +/- 8.4%) and 19 patients completed the study (10 placebo, 9 SB010. After 28 days, SB010 decreased the relative sputum eosinophil count (p = 0.004) as compared to no changes in placebo-treated patients. FENO, lung function, and symptoms were not affected significantly. We found an increase in blood IFN-gamma (p = 0.02) and a trend to lower IL-5 levels in patients treated with SB010. SB010 was safe and well tolerated. Thirty five AEs (22 SB010, 13 placebo including 1 SAE) were observed with 3 AEs in each group judged to be possibly treatment-related. CONCLUSION: In patients with eosinophilic COPD, sputum eosinophils could be reduced by inhalation of SB010. Long-term studies are needed to demonstrate clinical efficacy

Additional file 4: of A GATA3-specific DNAzyme attenuates sputum eosinophilia in eosinophilic COPD patients: a feasibility randomized clinical trial

Table S3 provides the baseline characteristics of the per-protocol population. Data are displayed as mean ± SD in the upper row, median (25% percentile – 75% percentile) in the lower row. Categorical variables are displayed as absolute numbers or percentage as indicated. (TIFF 185 kb