Many metalloenzymes that are key to bioenergetics are membrane enzymes, with canonical examples the complexes I, II, III and IV in the mitochondrial inner membrane. To study these enzymes in a native-like lipid membrane environment, we aim to develop novel bioelectrochemical techniques.

The primary goal of this research is to deepen our understanding of substrate-enzyme interactions in Glycoside hydrolases. For this purpose, Bacillus circulans xylanase (BcX) has been selected as a well-established model to examine the Michaelis complex and glycosyl-enzyme adduct.

Ever since the FDA approved the drug bedaquiline, which interferes with the bioenergetics of Mycobacterium tuberculosis by inhibiting the activity the F0F1-ATP synthase, respiratory-chain enzymes have been an active target space for the discovery of new antibiotics. To aid in this pursuit, we aim to…

Plastics are an intrinsic part of our society. Annually, 400Mt of plastics are produced of which roughly 40% is discarded within a year.

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

Can furan-based resisn be degraded by microbial enzymes in combination with mild pre-treatment?

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

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

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

How do lipases in Mycobacterium tuberculosis help the bacteria survive, and can we target them to create new antibiotics?

Learning from nature and utilizing microbial biodiversity to identify and characterize enzymes for degradation and upcycling of plastics and other polymeric materials.

Engineering an efficient microbial enzymatic polyethylene degradation pathway via an innovative combination of biochemistry and computational biology tools for enzyme discovery and characterization.

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

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.

This thesis explores how electron paramagnetic resonance (EPR) spectroscopy can be used to investigate key biochemical processes.

This thesis examines enzyme domain architecture and engineering to improve the breakdown of lignocellulose and starch, abundant biopolymers crucial for sustainable biofuel and biochemical production. Carbohydrate-active enzymes (CAZymes) facilitate this degradation, but the structural complexity of…

Hass

Developing safer alternatives to harmful PFAS filters and seeking new enzymes for medical applications. Two projects with Leiden researchers have been awarded funding through the Dutch Research Council's (NWO) Open Technology programme.

We aim to engineer streptomycetes to fully exploit their potential for natural product productions, by a rational design and evolution approach.

A European consortium has provided a disruptive technological breakthrough to allow the discovery and characterization of novel enzymes for industrial biotechnology. The technology will open the way to more efficient industrial processes such as in the biofuel, animal feed and paper and pulp industr…

This year, microbiologist Arthur Ram will start new research on producing useful enzymes in bulk. Ram receives an NWO grant for this project that will find its applications in the industrial biotechnology and food industry.

The Dutch organisation for scientific research NWO has announced that it will award an ENW-Klein grant to Marcellus Ubbink (LIC) for his research into the role of temperature in the evolution of enzymes. Sixteen grants have been awarded in total.

Promotor: Prof.dr. M. Danhof

This thesis describes research aimed at discovering inhibitors selective for either of the two endoplasmic reticulum α-glucosidases, ER-I and ER-II, with the overarching goal of discovering new antiviral agents to treat viruses that rely on host N-glycosylation for proliferation.

A team of researchers at the Institute of Biology Leiden, in collaboration with scientists from Utrecht University, has discovered a novel approach to improve the production of antibiotics and enzymes in the soil bacteria Streptomycetes.

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…

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

Researchers led by Professor of Chemistry Marcellus Ubbink have recently published a study in Proceedings of the National Academy of Sciences (PNAS) about the dynamics of an important redox enzyme. This work was accomplished thanks to an NWO VICI subsidy granted to Professor Ubbink.

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

Research in the Lars Jeuken group focusses on redox-active proteins and membranes enzymes, aiming to understand bacterial respiration at the molecular level for the development of antimicrobials and semi-artificial photo-synthetic cells.

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.

This thesis investigates how non-genetic factors, such as inflammation and concomitant medication, impact hepatic drug metabolism and subsequent drug metabolizing phenotype predictions.

Macromolecular Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University, comprising the PIs Marcellus Ubbink, Remus Dame, Lars Jeuken, Anne Wentink, Sebastian Geibel, Anjali Pandit, René Olsthoorn, Alia, and Steffen Brünle.

From descriptive to physiological models that can predict oral absorption and elimination of CYP3A substrates across the pediatric age range.

Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive.

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'.

This thesis focuses on the design and synthesis of activity-based probes and inhibitors targeting enzymes involved in the degradation of specific plant glycans.

How can we develop new chemical biology tools and approaches to understand and interfere with glucosylceramide metabolism in relation to Gaucher disease?

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.

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.

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

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.

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

Research projects for students of the University of Leiden and other Dutch Universities are often available at the MacBio group. The research lines are also described in the Research section. For details of specific projects contact the supervisor (Ubbink, Dame, Boyle, Jeuken or Wentink).

Research at the BIOSYN group is comprised of the following research themes:

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…

How do protein modifications work together to repair DNA, and what can we learn about these interactions to better understand disease?