biosensors Review Yeast-Based Biosensors: Current Applications and New Developments Helene Martin-Yken 1,2,3,4 1 Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), UMR 792 Toulouse Biotechnology Institute (TBI), 31400 Toulouse, France; [email protected]; Tel.: +689-89-52-31-88 2 Institut de Recherche pour le Développement (IRD), Faa’a, 98702 Tahiti, French Polynesia 3 Unite Mixte de Recherche n◦241 Ecosystemes Insulaires et Oceaniens, Université de la Polynésie Française, Faa’a, 98702 Tahiti, French Polynesia 4 Laboratoire de Recherche sur les Biotoxines Marines, Institut Louis Malardé, Papeete, 98713 Tahiti, French Polynesia Received: 1 April 2020; Accepted: 20 April 2020; Published: 13 May 2020 Abstract: Biosensors are regarded as a powerful tool to detect and monitor environmental contaminants, toxins, and, more generally, organic or chemical markers of potential threats to human health. They are basically composed of a sensor part made up of either live cells or biological active molecules coupled to a transducer/reporter technological element. Whole-cells biosensors may be based on animal tissues, bacteria, or eukaryotic microorganisms such as yeasts and microalgae. Although very resistant to adverse environmental conditions, yeasts can sense and respond to a wide variety of stimuli. As eukaryotes, they also constitute excellent cellular models to detect chemicals and organic contaminants that are harmful to animals. For these reasons, combined with their ease of culture and genetic modification, yeasts have been commonly used as biological elements of biosensors since the 1970s. This review aims first at giving a survey on the different types of yeast-based biosensors developed for the environmental and medical domains. We then present the technological developments currently undertaken by academic and corporate scientists to further drive yeasts biosensors into a new era where the biological element is optimized in a tailor-made fashion by in silico design and where the output signals can be recorded or followed on a smartphone. Keywords: yeasts; biosensors; cell signaling; environmental contaminants; detection 1. Introduction Biosensors are among the most sensitive screening methods used to detect harmful chemicals and pollutants. According to their classically accepted definition, biosensors are composed of a biological recognition element able to sense or interact with the target molecules coupled to a physicochemical transducer and a microelectronic processor functioning as amplifiers and converters of the biological response into a measurable/numerical signal [1]. In these devices, the biological elements can be antibodies, specific proteins such as cell receptors or enzymes, nucleic acids, organelles, tissues, microorganisms, or whole cells. In this last category the whole cells, either eukaryotic or prokaryotic, are used as reporters with the advantage of combining both the biological receptor and the transducer elements in one [2]. Cells or micro-organisms used as whole-cell biosensors can be genetically modified in various ways in order to increase their sensitivity or to incorporate different reporter and transducer capacity [3,4]. Most biosensors have been developed based on bacterial cells; however, eukaryotic cellular models present several relevant advantages. Among them, yeasts are of special interest, given their resistance to harsh environmental conditions, their successful long-term relationship with humans [5], Biosensors 2020, 10, 51; doi:10.3390/bios10050051 www.mdpi.com/journal/biosensors Biosensors 2020, 10, 51 2 of 19 Biosensors 2020, 10, x FOR PEER REVIEW 2 of 19 and the fact that they are very well known at both technological and genetic levels. As eukaryotic resistance to harsh environmental conditions, their successful long-term relationship with humans organisms, yeasts share most cellular features and molecular mechanisms with our mammalian cells [5], and the fact that they are very well known at both technological and genetic levels. As eukaryotic andorganisms, notably severalyeasts share signaling most cellular pathways features which and are molecular of great mechanisms relevance towards with our sensingmammalian and cells responding toand environmental notably several stimuli. signaling This pathways high level which of are conservation of great relevance has long towards driven sensing scientists and responding to use yeasts as modelto environmental eukaryotes stimuli. for the This study high of level a wide of conservation range of cellular has long biology driven processesscientists to [ 6use]. The yeasts best as studied amongmodel yeasts eukaryotes species, for theSaccharomyces study of a wide cerevisiae range (alsoof cellular known biology as bakers’ processes yeast) [6]. wasThe thebest firststudied eukaryotic organismamong yeasts whose species, genome Saccharomyces was entirely cerevisiae sequenced (also known [7] and as bakers’ is remarkably yeast) was easy the tofirst modify eukaryotic genetically. Yeastsorganism grow whose fast on genome inexpensive was entirely culture sequenced medium. [7] They and is are remarkably very robust easy organisms to modify that genetically. tolerate a wide rangeYeas ofts grow temperatures, fast on inexpensive and they culture can be medium. frozen or They dehydrated are very robust for storage organisms and that transportation tolerate a wide purposes. range of temperatures, and they can be frozen or dehydrated for storage and transportation purposes. The combination of these elements (conservation of eukaryotic pathways and cellular mechanisms) The combination of these elements (conservation of eukaryotic pathways and cellular mechanisms) with the practical aspects such as safety and easiness to cultivate, transport, and conserve yeast cells with the practical aspects such as safety and easiness to cultivate, transport, and conserve yeast cells makesmakes them them an an extremely extremely interestinginteresting choice choice of of biological biological model model for for the the development development of biosensors of biosensors [5]. In[5] addition,. In addition, from from an an ethical ethical point point ofof view,view, the the choice choice of ofyeast yeast cells cells also alsoallows allows using non using-animal non-animal modelsmodels to to determine determine thethe potentiallypotentially toxic toxic effects effects of of very very diverse diverse compounds compounds or inversely or inversely to screen to screen for therapeuticfor therapeutic molecules molecules (see below).(see below). Bioassays Bioassays and and biosensors biosensor baseds based on on yeast yeast cells cells have have been been emerging overemerging the years over and the areyears actually and are in actually use in variousin use in domainsvarious domains of application. of application. In this In review, this review, we describe we the diffdescribeerent types the different of biosensors types of based biosensors on yeast based cells on yeast with cells a special with a focus special on focus environmental on environmental and medical applications;and medical this applica distinction,tions; this however, distinction is sometime, however, hardis sometime to make hard and canto make appear and arbitrary can appear since what arbitrary since what makes environmental contaminants harmful to Man or wild-life is precisely their makes environmental contaminants harmful to Man or wild-life is precisely their effects on health. effects on health. Hence, some biosensors or yeast-based screens described in this review can be Hence, some biosensors or yeast-based screens described in this review can be considered as relevant considered as relevant for both of these application domains. Figure 1 depicts the general principle forof both yeast of-based these biosensors, application with domains. the possible Figure inputs,1 depicts the the sensing general and principle detection of elements yeast-based, and biosensors,the withdesired the possibleoutput response. inputs, the sensing and detection elements, and the desired output response. FigureFigure 1. 1.General General scheme of of aa yeast yeast biosensor biosensor’s’s purpose purpose and andfunctioning. functioning. Different Di ffpossibleerent possible inputs inputs appearappear on on the the left,left, in a non non-exhaustive-exhaustive list. list. Live Live yeast yeast cells cells are represented are represented by a budding by a budding yeast shape yeast shape insideinside of of a a supporting supporting structure structure that that is iscoupled coupled to the to thesignal signal detection detection system. system. Three main Three outputs main outputsare are generallygenerally sought sought afterafter byby designersdesigners and and users: users: either either a “yes/no” a “yes/no” answer answer in case in case a threshold a threshold levellevel of of the targetthe target molecule(s) molecule(s) exists, exists, or aor quantification a quantification value value whenwhen needed and and possible. possible. First,First, yeast yeast cellscells either native native or or modified modified to constitutively to constitutively produce produce luminescence luminescence can be used can beas used as non-specificnon-specific reporter reporter systems systems to to monitor monitor the thetoxicity toxicity toward toward eukaryotic eukaryotic cells of compounds cells of compounds found or found used in food, the environment, building materials, cosmetology, drug design, etc. [8].