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      “Fight-flight-or-freeze” – how Yarrowia lipolytica responds to stress at molecular level?

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          Abstract

          Abstract

          Yarrowia lipolytica is a popular yeast species employed in multiple biotechnological production processes. High resistance to extreme environmental conditions or metabolic burden triggered by synthetically forced over-synthesis of a target metabolite has its practical consequences. The proud status of an “industrial workhorse” that Y. lipolytica has gained is directly related to such a quality of this species. With the increasing amount of knowledge coming from detailed functional studies and comprehensive omics analyses, it is now possible to start painting the landscape of the molecular background behind stress response and adaptation in Y. lipolytica. This review summarizes the current state-of-art of a global effort in revealing how Y. lipolytica responds to both environmental threats and the intrinsic burden caused by the overproduction of recombinant secretory proteins at the molecular level. Detailed lists of genes, proteins, molecules, and biological processes deregulated upon exposure to external stress factors or affected by over-synthesis of heterologous proteins are provided. Specificities and universalities of Y. lipolytica cellular response to different extrinsic and intrinsic threats are highlighted.

          Key points

          • Y. lipolytica as an industrial workhorse is subjected to multiple stress factors.

          • Cellular responses together with involved genes, proteins, and molecules are reviewed.

          • Native stress response mechanisms are studied and inspire engineering strategies.

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          Most cited references97

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          Genomic Expression Programs in the Response of Yeast Cells to Environmental Changes

          We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.
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            Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system.

            The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast.
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              Yarrowia lipolytica: safety assessment of an oleaginous yeast with a great industrial potential.

              Yarrowia lipolytica has been developed as a production host for a large variety of biotechnological applications. Efficacy and safety studies have demonstrated the safe use of Yarrowia-derived products containing significant proportions of Yarrowia biomass (as for DuPont's eicosapentaenoic acid-rich oil) or with the yeast itself as the final product (as for British Petroleum's single-cell protein product). The natural occurrence of the species in food, particularly cheese, other dairy products and meat, is a further argument supporting its safety. The species causes rare opportunistic infections in severely immunocompromised or otherwise seriously ill people with other underlying diseases or conditions. The infections can be treated effectively by the use of regular antifungal drugs, and in some cases even disappeared spontaneously. Based on our assessment, we conclude that Y. lipolytica is a "safe-to-use" organism.
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                Author and article information

                Contributors
                ewelina.celinska@up.poznan.pl
                Journal
                Appl Microbiol Biotechnol
                Appl Microbiol Biotechnol
                Applied Microbiology and Biotechnology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0175-7598
                1432-0614
                30 April 2022
                30 April 2022
                2022
                : 106
                : 9-10
                : 3369-3395
                Affiliations
                GRID grid.410688.3, ISNI 0000 0001 2157 4669, Department of Biotechnology and Food Microbiology, , Poznan University of Life Sciences, ; Wojska Polskiego 48, 60-627 Poznan, Poland
                Author information
                http://orcid.org/0000-0001-8372-8459
                Article
                11934
                10.1007/s00253-022-11934-x
                9151528
                35488934
                c87518cc-dd20-4a79-ba66-3d5bb0c2bf18
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 March 2022
                : 14 April 2022
                : 20 April 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004281, Narodowe Centrum Nauki;
                Award ID: 2021/41/B/NZ9/00086
                Award Recipient :
                Categories
                Mini-Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2022

                Biotechnology
                stress response,environmental stress,metabolic burden,heterologous protein,recombinant protein secretion,yeast

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