A5041317444- Lysosomal Storage Disorders Research
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- Biofuel production and bioconversion
- Metabolism and Genetic Disorders
- Trypanosoma species research and implications
- Carbohydrate Chemistry and Synthesis
- Glycogen Storage Diseases and Myoclonus
- Enzyme Production and Characterization
- Enzyme Catalysis and Immobilization
- Fungal Biology and Applications
- Mitochondrial Function and Pathology
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Amino Acid Enzymes and Metabolism
- Genomics and Rare Diseases
- Neonatal Health and Biochemistry
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- Biomedical Research and Pathophysiology
- Diet and metabolism studies
- Nanoplatforms for cancer theranostics
- Ocular Oncology and Treatments
- Photosynthetic Processes and Mechanisms
Erasmus MC
2015-2024
Erasmus University Rotterdam
2010-2023
Rotterdam University of Applied Sciences
2022-2023
Erasmus MC - Sophia Children’s Hospital
2013
Wageningen University & Research
2000-2007
Leiden University
2006
Leiden University Medical Center
2005
University of Southern Denmark
2004
Graduate School Experimental Plant Sciences
1994-1999
University of Amsterdam
1990-1993
The external pH appeared to be the main factor governing oxalic acid production by Aspergillus niger. A glucose-oxidase-negative mutant produced substantial amounts of as long culture was 3 or higher. When decreased below 2, no formed. activity oxaloacetate acetylhydrolase (OAH), enzyme believed responsible for oxalate formation in A. niger, correlated with production. OAH purified from niger and characterized. cleaves acetate, but never accumulated any acetate broth. Since an acuA mutant,...
Trehalose is a non-reducing disaccharide found at high concentrations in Aspergillus nidulans conidia and rapidly degraded upon induction of conidial germination. Furthermore, trehalose accumulated response to heat shock or an oxidative shock. The authors have characterized the A. tpsA gene encoding trehalose-6-phosphate synthase, which catalyses first step biosynthesis. Expression Saccharomyces cerevisiae tps1 mutant revealed that product functional equivalent yeast Tps1 synthase. tpsA-null...
ABSTRACT d -Mannitol is the predominant carbon compound in conidiospores of filamentous fungus Aspergillus niger and makes up 10 to 15% dry weight. A number physiological functions have been ascribed mannitol, including serving as a reserve source, an antioxidant, store reducing power. In this study, we cloned characterized A. mpdA gene, which encodes mannitol 1-phosphate dehydrogenase (MPD), first enzyme biosynthesis pathway. The promoter contains putative binding sites for...
Abstract Objective Mucopolysaccharidosis (MPS) IIIA (Sanfilippo syndrome type A) is a lysosomal storage disorder caused by deficiency of the enzyme sulfamidase. Information on natural course MPS scarce, but much needed in view emerging therapies. Methods Clinical history and molecular defects all 110 patients identified enzymatic studies Netherlands were collected included this study. Results First clinical signs, mainly consisting delayed speech development behavioral problems, noted...
Background ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, mutations were shown to cause new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective this study was describe family with 2 siblings affected by different dystonic disorders resulting phenotype mutations. Methods Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, protein expression...
A sugar-transporter-encoding gene, mstA, which is a member of the major facilitator superfamily, has been cloned from genomic DNA library filamentous fungus Aspergillus niger. To enable functional characterization MSTA, full-length cDNA was expressed in Saccharomyces cerevisiae strain deficient hexose uptake. Uptake experiments using 14C-labelled monosaccharides demonstrated that although able to transport D-fructose ( K(m), 4.5+/-1.0 mM), D-xylose 0.3+/-0.1 mM) and D-mannose 60+/-20...
Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of endoplasmic reticulum (ER), two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration...
We report the progress of a multi-disciplinary research project on solid-state fermentation (SSF) filamentous fungus Aspergillus oryzae. The molecular and physiological aspects in submerged (SmF) SSF are compared we observe number differences correlated with different growth conditions. First, aerial hyphae which occur only SSFs mainly responsible for oxygen uptake. Second, is characterised by gradients temperature, water activity nutrient concentration, inside polyols accumulating. Third,...
Intracellular pH homeostasis in the filamentous fungus Aspergillus niger was measured real time by 31 P NMR during perfusion tube of fungal biomass immobilized Ca 2+ ‐alginate beads. The maintained constant cytoplasmic (pH cyt ) and vacuolar vac values 7.6 6.2, respectively, when extracellular ex varied between 1.5 7.0 presence citrate. metabolism did not collapse until a ΔpH over membrane 6.6–6.7 reached 0.7–0.8). Maintenance these large differences possible without increased respiration...
Aspergillus niger mutants relieved of carbon repression were isolated from an areA parental strain by selection colonies that exhibited improved growth on a combination 4-aminobutanoic acid (GABA) and D-glucose. In addition to derepression the utilization GABA as nitrogen source in presence D-glucose, three four also showed L-alanine L-proline utilization. Transformation with A. creA gene, encoding repressor protein CREA, re-established phenotype GABA/D-glucose, identifying mutations creAd....
The role of hexose phosphorylating enzymes in the signaling carbon catabolite repression was investigated filamentous fungus Aspergillus nidulans. A d-fructose non-utilizing, hexokinase-deficient (hxkA1, formerly designated frA1) strain utilized to obtain new mutants lacking either glucokinase (glkA4) or both kinases (hxkA1/glkA4). d-Glucose and phosphorylation is completely abolished double mutant, which consequently cannot grow on sugar. single mutant exhibits no nutritional deficiencies....
Polyol accumulation and metabolism were examined in Aspergillus oryzae cultured on whole wheat grains or dough as a model for solid-state culture. In fermentation (SSF), water activity (a(w)) is typically low resulting osmotic stress. addition to high level of mannitol, which always present the cells, A. accumulated concentrations glycerol, erythritol arabitol at relatively a(w) (0.96-0.97) SSF. Accumulation such mixture polyols rather unusual might be typical mycelium accumulating various...
Congenital disorders of glycosylation comprise a group genetic defects with high frequency intellectual disability, caused by deficient proteins and lipids. The molecular basis the majority congenital type I subtypes, localized in cytosol endoplasmic reticulum, has been solved. However, elucidation causative genes for defective Golgi (congenital II) remains challenging because lack sufficiently specific diagnostic serum methods. In single patient whole-exome sequencing revealed MAN1B1 as...
Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome; MPS VI) is an autosomal recessive lysosomal storage disorder in which deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B; ARSB) leads to the glycosaminoglycans (GAGs) connective tissue. The genotype-phenotype correlation has been addressed several publications but picture not complete. Since 2007, enzyme-replacement therapy (ERT) available for patients with Netherlands. purpose our study was learn more about correlations...
Routine diagnostic screening of inborn errors metabolism (IEM) is currently performed by different targeted analyses known biomarkers. This approach time-consuming, targets a limited number biomarkers and will not identify new Untargeted metabolomics generates global metabolic phenotype has the potential to overcome these issues. We describe novel, single platform, untargeted method for IEM, combining semi-automatic sample preparation with pentafluorophenylpropyl phase (PFPP)-based UHPLC-...
Sphingolipidoses are severe, mostly infantile lysosomal storage disorders (LSDs) caused by defective glycosphingolipid degradation. Two of these sphingolipidoses, Tay Sachs and Sandhoff diseases, β-Hexosaminidase (HEXB) enzyme deficiency, resulting in ganglioside (GM2) accumulation neuronal loss. The precise sequence cellular events preceding, leading to, neuropathology remains unclear, but likely involves inflammation GM2 multiple cell types. We aimed to determine the consequences Hexb...