## 1 Introduction  
The cellobiose dehydrogenase (CDH; EC 1.1.99.18) is a monomeric, an extracellular hemoflavoprotein with two domains, flavin and heme domain, connected via flexible peptide linker [1]. CDH catalyzes the oxidation of the reducing end of cellobiose and other \(\beta\)-1,4-linked disaccharideswith a \(\beta\)-glucose moiety, to their corresponding lactones [2]. Different electron acceptors can reoxidize the reduced enzyme, such as 2,6-dicholoro-indophenol (DCIP), or metal ions, for example Fe(III) or even oxygen, albeit the latter is a very poor electron acceptor [2]. Although diverse of white-rot and other fungi have been reported to secret CDH, and a lot have been purified and characterized, the in vivo function of CDH is not sufficiently understood [3]. It has been suggested that CDH plays a role in lignocellulosic biomass hydrolysis, such as relief of product inhibition of cellulases by oxidation of cellobiose, generation of peroxide for inhibition of opposing microbes, and regeneration of redox metal ions (such as Fe\({}^{2+}\)) to sustain the Fenton-type chemistry that produces hydroxyl radicals who can modify polysaccharides causing partial hydrolysis and swelling of insoluble fibers which helps breakdown of lignocellulosic by glycoside hydrolase [1; 2; 3]. Due to its properties, CDH has been applied in biosensors for detection of lactose, in enzymatic biofuel cells as anode catalyst [4; 5], for lactobionic acid production [6], dye removal [7], and bioremediation [1]. Improvement of activity and stability of CDH would benefit all of these applications and directed evolution based on random introduction of mutations resulting in a protein library, where mutants having desired properties can be screened is used very often [8]. In order to make screening process more efficient during directed evolution, various expression systems that keep connection between genotype and phenotype are developed, such as phage [9], bacterial [10], yeast [11], and mammalian cell display [12]. The advantage of yeast display is the existence of eukaryotic protein production machinery that is essential for post-translational modifications of expressed proteins [8] and compatibility with flow cytometric analysis, which allows quantitative measurements of equilibrium binding constants, dissociation kinetics, and specificity of the displayed proteins without requisite of soluble protein expression and purification [13]. Screening methods usually involve phenotypic selection based on colorimetric or fluorometric assays in microtiter plates (MTPs) [14] and solid-phase screening on agar plates or membranes [15]. Regardless, during colony screening on solid-phase, or individual clones in MTPs, usually \(10^{3}\)-\(10^{5}\) clones and seldom more than \(10^{6}\) can be screened with sophisticated automated systems [16]. One of emerging ultra-high-throughput screening systems to this day is fluorescence-activated cell sorting (FACS) which can routinely sort \(>\)\(10^{7}\) cells/h, if there is an appropriate fluorescence assay [17; 18]. Resazurin (7-hydroxy-3H-phenoxazin-3-one-10-oxide) is a tetrazolium-based, non-toxic, water-soluble dye that can be reduced by cellular metabolic activity to the highly fluorescent resorufin [19]. Resazurin also changes color from blue to pink upon reduction [20]. This reduction causes the loss of an oxygen atom loosely bound to the nitrogen of the phenaxazine nucleus. Atmospheric oxygen cannot reverse this change and it is mostly independent of both oxygen content and reduction potential [19]. Resazurin has been used to examine the viability of microorganisms (non-destructively) [21], for biofilm quantification [22], and anti-biofilm disinfectant testing of clinical devices [23]. Several intracellular oxidoreductase, for instance diaphragases and NADH dehydrogenase, were reported to be responsible for the reduction of resazurin to resorufin during cell viability assay [24].