This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: J.D.C. Codee

Promotor: G.P. van Wezel, Co-Promotor: E. Vijgenboom

Promotor: G.P. van Wezel, Co-promotor: D. Claessen

Hoe kan de techniek van cell wall engineering worden ingezet zodat de industrie streptomyceten beter kunnen verwerken tot nieuwe antibiotica?

Salicylic acid (SA) is a plant hormone, which is involved in the defense responses to pathogens and to abiotic stress, and in the regulation of plant growth and development.

Promotor: Prof.dr. M. Danhof

The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic…

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

Promotores: Prof.dr. G.W. Canters, Prof.dr. T.J. Aartsma

Neuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms.

An objective of this research was to achieve direct, well-defined and non-rate-limiting electron transfer between respiratory enzymes and the electrode surface by means of 'Q-wires'.

Phospholipase A/acyltransferase 3 (PLAAT3) and PLAAT4 are enzymes involved in the synthesis of bioactive lipids. Despite sequential and structural similarities, the two enzymes differ in activity and specificity.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-promotor: B.I. Florea

Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency

The growing demand of energy indicates that global energy resources in the form of fossil fuels will not be sufficient in the future. In order to solve potential future energy problems development of a sustainable hydrogen economy is highly desirable.

The recently introduced nature-originated deep eutectic solvents, so-called natural deep eutectic solvents (NADES) are considered as truly green solvents, which composed of natural ingredients found abundantly in organisms.

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases.

In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

Almost all bacteria are enveloped by a cell wall that provides cellular protection.

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

Promotor: B.van de Water, Co-promotor: L.S.Price

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Promotie

The work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide Pel, generated by Pseudomonas aeruginosa.

Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

The studies described in this thesis deal with glycosidases, in particular alpha-galactosidases.

The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide.

Promotor: Prof.dr. M. Ubbink

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

Plants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions.

Promotie

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

Promotores: Prof.dr. H. van Veen & Prof.dr. W. de Boer (Wageningen University)

Streptomyces present a valuable platform for natural product discovery. Lugdunomycin is a novel angucycline-derived polyketide from Streptomyces sp QL37, with unprecedented skeleton and antimicrobial activity.

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

Promotor: Prof.dr. G.P. van Wezel

Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

Agrobacterium tumefaciens, a gram-negative plant pathogen belonging to the family Rhizobiaceae, is the causative agent of crown gall disease, which can affect many plant species including agronomically important ones.

Promotores: G.W. Canters, T.J. Aartsma

Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.