Biological and technical challenges for implementation of yeast-based biosensors

Abstract

Biosensors are low-cost and low-maintenance alternatives to conventional analytical techniques for biomedical, industrial and environmental applications. Biosensors based on whole microorganisms can be genetically engineered to attain high sensitivity and specificity for the detection of selected analytes. While bacteria-based biosensors have been extensively reported, there is a recent interest in yeast-based biosensors, combining the microbial with the eukaryotic advantages, including possession of specific receptors, stability and high robustness. Here, we describe recently reported yeast-based biosensors highlighting their biological and technical features together with their status of development, that is, laboratory or prototype. Notably, most yeast-based biosensors are still in the early developmental stage, with only a few prototypes tested for real applications. Open challenges, including systematic use of advanced molecular and biotechnological tools, bioprospecting, and implementation of yeast-based biosensors in electrochemical setup, are discussed to find possible solutions for overcoming bottlenecks and promote real-world application of yeast-based biosensors.

FIGURE 1

Transduction mechanisms of yeast‐based biosensors. Different yeast species, genetically modified or not, can act as transducers for the sensing and quantification of many analytes. Cell surface receptors and plasma membrane transporters are involved in the first interaction between the cell and the analyte. The output signals can be quantified through: amperometric/voltammetric measurements by means of intracellular metabolic redox reactions and redox mediators; cell growth inhibition and/or cell death by means of inhibition of metabolic regulatory proteins; optical measurements by means of the regulated activity of constitutive or inducible promoters fused to selected reporter genes and related proteins

FIGURE 2

Yeast‐based biosensors: From laboratory stage to commercial device. Different yeast species, including Saccharomyces cerevisiae, Arxula adeninivorans and Candida albicans, can function as sensing elements for a variety of analytes. The transduction mechanisms can be essentially optical or electrochemical with relative specific read‐out. The elaboration of the signal processing can be adaptable to economical portable devices and/or Internet of Things systems. Approximately, one hundred yeast biosensors have been developed at laboratory stage, while the prototypes are very limited, about five. Apparently, only one yeast biosensor commercial device is available

FIGURE 3

Yeast‐based biosensors prototypes: Working concepts and devices. (A) Yestrosens, a field‐portable and storable S. cerevisiae biosensor device for the detection of endocrine‐disrupting chemicals (B) Engineered S. cerevisiae cells for on‐site pathogen surveillance adapted to develop a rapid dipstick test which produces either a yes/no response by visual inspection or a quantitative measure by pixel colour analysis (C) EstraMonitor, based on immobilized recombinant A. adeninivorans cells contained in measuring chambers for electro‐chemical detection of total estrogenic activity. Selected images are reproduced with permission from the references Lobsiger et al., ; Ostrov et al., ; Pham et al.,