Yarrowia lipolytica strains and their biotechnological applications: how natural biodiversity and metabolic engineering could contribute to cell factories improvement

Abstract

Among non-conventional yeasts of industrial interest, the dimorphic oleaginous yeast Yarrowia lipolytica appears as one of the most attractive for a large range of white biotechnology applications, from heterologous proteins secretion to cell factories process development. The past, present and potential applications of wild type, traditionally improved or genetically modified Yarrowia lipolytica strains will be resumed, together with the wide array of molecular tools now available to genetically engineer and metabolically remodel this yeast. The present review will also provide a detailed description of Yarrowia lipolytica strains and highlight the natural biodiversity of this yeast, a subject little touched upon in most previous reviews. This work intends to fill this gap by retracing the genealogy of the main Yarrowia lipolytica strains of industrial interest, by illustrating the search for new genetic backgrounds and by providing data about the main publicly available strains in yeast collections worldwide. At last, it will focus on exemplifying how advances in engineering tools can leverage a better biotechnological exploitation of the natural biodiversity of Yarrowia lipolytica and of other yeasts from the Yarrowia clade.

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“…Yarrowia lipolytica , an oil-producing yeast, has attracted much attention due to its ability to accumulate high lipid content using a variety of substrates and its flexibility in genetic manipulation [ 248 ]. The intracellular lipid metabolism in Yarrowia lipolytica was customized to produce fatty acids, which are renewable lipid chemicals and precursors for the production of a new generation of biofuels [ 249 ].…”

Study of the persistence and dynamics of recombinant mCherry‐producing Yarrowia lipolytica strains in the mouse intestine using fluorescence imaging

“…Yeasts combine the ease of use of microorganisms with a eukaryotic organization enabling post‐translational protein modification and suitable glycosylation, which makes them preferred over other microbial systems for the production of recombinant therapeutic proteins (Ivanova, 2021; Kim et al, 2015; Lee et al, 2015; Madhavan et al, 2021; Patra et al, 2021; Pöhlmann et al, 2013). Y. lipolytica is a dimorphic oleaginous yeast that has drawn the attention of industrialists in the 1950s and has since been recognized as a powerful host for the expression, secretion and surface display of heterologous proteins, as well as a promising source of engineered cell factories for a wide range of applications (Madzak, 2018, 2021a). This non‐conventional yeast is a biosafety level 1 microorganism with a documented use in food (International Dairy Federation/European Food and Feed Cultures Association) and a GRAS (generally recognized as safe) status (USA Food and Drug Administration) (Groenewald et al, 2014; Madzak, 2021a).…”

“…Y. lipolytica is a dimorphic oleaginous yeast that has drawn the attention of industrialists in the 1950s and has since been recognized as a powerful host for the expression, secretion and surface display of heterologous proteins, as well as a promising source of engineered cell factories for a wide range of applications (Madzak, 2018, 2021a). This non‐conventional yeast is a biosafety level 1 microorganism with a documented use in food (International Dairy Federation/European Food and Feed Cultures Association) and a GRAS (generally recognized as safe) status (USA Food and Drug Administration) (Groenewald et al, 2014; Madzak, 2021a). The European Food and Safety Authority allowed in 2019 the use of Y. lipolytica biomass as a novel food for human consumptions thanks to its safety and nutritional advantages (Jach & Malm, 2022).…”

“…Industrial good manufacturing practices production platforms based on engineered Y. lipolytica have been developed since the 2000s and include new white biotechnological applications, for example as a functional feed additive for animals or a source of human milk oligosaccharide for infant milk formulations (Guardiola et al, 2021; Madzak, 2021a). Y. lipolytica biomass from a proprietary wild‐type strain is commercialized as fodder yeast for farm and pet animals by Skotan SA (Chorzów, Poland), a company that also develops prebiotic/probiotic applications for this yeast (Jach & Malm, 2022; Madzak, 2021a; Zinjarde, 2014). Indeed, several in vivo studies reported probiotic properties of this yeast in mammals, birds, fish, crustaceans and molluscs (Guardiola et al, 2021).…”

“…Since several decades, Y. lipolytica has been engineered to produce human compatible therapeutic proteins such as blood coagulation factor XIIIa, epidermal growth factor and single‐chain antibodies (Darvishi et al, 2019; Espejo‐Mojica et al, 2015; Gasmi et al, 2011; Hamsa et al, 1998; Madzak, 2021a; Madzak & Beckerich, 2013; Swennen et al, 2002; Tharaud et al, 1992; Tiels et al, 2012). Several Y. lipolytica strains have been engineered through deletion of their yeast‐specific mannosyltransferases and over and/or heterologous expression of other enzymes of the glycosylation pathways, to produce more human‐compatible glycoproteins (De Pourcq, Tiels, et al, 2012; De Pourcq, Vervecken, et al, 2012).…”