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LudwigLab Biocatalysis & Biosensing Research Group

Thomas Reichhart, MSc

Background

Cellobiose dehydrogenase (CDH) is a fungal flavocytochrome with a unique bipartite protein structure consisting of a catalytic active dehydrogenase (DH) domain connected via a flexible linker to a mobile cytochrome C (CYT) domain (Figure 2). This special dual structure enables CDH to catalyse the oxidation of glucose via its DH domain, and subsequently perform a direct electron transfer (DET) step using the mobile CYT domain. In this way, electrons are efficiently directed towards a terminal electron acceptor, without the need of an intermediary electron mediator. The capacity of CDH to perform DET renders it a promising candidate for incorporation as a biorecognition element (BRE) into implantable blood glucose biosensors.

PhD Project

In my PhD project, I will develop next-generation cellobiose dehydrogenase (CDH) with improved properties to use as biorecognition elements for implantable blood glucose biosensors. There are, in particular, four highly desired properties:

(1)   Improved glucose turnover rates to further enhance the signal intensity for precise and accurate detection of blood glucose levels

(2)   Decreased cross-reactivity towards disaccharides to increase signal-to-noise ratios and overall sensitivity of the biosensor

(3)   Suppressed oxygen reactivity to expand the long-term operational stability of the enzyme, even in highly enriched oxygen environments such as human blood

(4)   Switchable activity for remote control and improved long-term stability of the implantable biosensor device (see Figure above)

Funding

My PhD project, titled “Switchable cellobiose dehydrogenase,” is financed by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Scholarship (Grant agreement No. 813006).