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      Response mechanisms of Saccharomyces cerevisiae to the stress factors present in lignocellulose hydrolysate and strategies for constructing robust strains

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          Abstract

          Bioconversion of lignocellulosic biomass to biofuels such as bioethanol and high value-added products has attracted great interest in recent decades due to the carbon neutral nature of biomass feedstock. However, there are still many key technical difficulties for the industrial application of biomass bioconversion processes. One of the challenges associated with the microorganism Saccharomyces cerevisiae that is usually used for bioethanol production refers to the inhibition of the yeast by various stress factors. These inhibitive effects seriously restrict the growth and fermentation performance of the strains, resulting in reduced bioethanol production efficiency. Therefore, improving the stress response ability of the strains is of great significance for industrial production of bioethanol. In this article, the response mechanisms of S. cerevisiae to various hydrolysate-derived stress factors including organic acids, furan aldehydes, and phenolic compounds have been reviewed. Organic acids mainly stimulate cells to induce intracellular acidification, furan aldehydes mainly break the intracellular redox balance, and phenolic compounds have a greater effect on membrane homeostasis. These damages lead to inadequate intracellular energy supply and dysregulation of transcription and translation processes, and then activate a series of stress responses. The regulation mechanisms of S. cerevisiae in response to these stress factors are discussed with regard to the cell wall/membrane, energy, amino acids, transcriptional and translational, and redox regulation. The reported key target genes and transcription factors that contribute to the improvement of the strain performance are summarized. Furthermore, the genetic engineering strategies of constructing multilevel defense and eliminating stress effects are discussed in order to provide technical strategies for robust strain construction. It is recommended that robust S. cerevisiae can be constructed with the intervention of metabolic regulation based on the specific stress responses. Rational design with multilevel gene control and intensification of key enzymes can provide good strategies for construction of robust strains.

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          Pretreatment of lignocellulose: Formation of inhibitory by-products and strategies for minimizing their effects.

          Biochemical conversion of lignocellulosic feedstocks to advanced biofuels and other commodities through a sugar-platform process involves a pretreatment step enhancing the susceptibility of the cellulose to enzymatic hydrolysis. A side effect of pretreatment is formation of lignocellulose-derived by-products that inhibit microbial and enzymatic biocatalysts. This review provides an overview of the formation of inhibitory by-products from lignocellulosic feedstocks as a consequence of using different pretreatment methods and feedstocks as well as an overview of different strategies used to alleviate problems with inhibitors. As technologies for biorefining of lignocellulose become mature and are transferred from laboratory environments to industrial contexts, the importance of management of inhibition problems is envisaged to increase as issues that become increasingly relevant will include the possibility to use recalcitrant feedstocks, obtaining high product yields and high productivity, minimizing the charges of enzymes and microorganisms, and using high solids loadings to obtain high product titers.
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            Remodeling of yeast genome expression in response to environmental changes.

            We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in temperature, oxidation, nutrients, pH, and osmolarity. The results demonstrate that more than half of the genome is involved in various responses to environmental change and identify the global set of genes induced and repressed by each condition. These data implicate a substantial number of previously uncharacterized genes in these responses and reveal a signature common to environmental responses that involves approximately 10% of yeast genes. The results of expression analysis with MSN2/MSN4 mutants support the model that the Msn2/Msn4 activators induce the common response to environmental change. These results provide a global description of the transcriptional response to environmental change and extend our understanding of the role of activators in effecting this response.
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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.

                Author and article information

                Contributors
                zhaoxb@mail.tsinghua.edu.cn
                Journal
                Biotechnol Biofuels Bioprod
                Biotechnol Biofuels Bioprod
                Biotechnology for Biofuels and Bioproducts
                BioMed Central (London )
                2731-3654
                15 March 2022
                15 March 2022
                2022
                : 15
                : 28
                Affiliations
                [1 ]GRID grid.12527.33, ISNI 0000 0001 0662 3178, Key Laboratory of Industrial Biocatalysis, Ministry of Education, , Tsinghua University, ; Beijing, 100084 China
                [2 ]GRID grid.12527.33, ISNI 0000 0001 0662 3178, Institute of Applied Chemistry, Department of Chemical Engineering, , Tsinghua University, ; Beijing, 100084 China
                Author information
                http://orcid.org/0000-0002-4094-268X
                Article
                2127
                10.1186/s13068-022-02127-9
                8922928
                35292082
                8da81e9c-534f-4ff9-bb19-a9baee413a15
                © 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/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 6 December 2021
                : 1 March 2022
                Funding
                Funded by: National Key R & D Program of China
                Award ID: 2018YFA0902200
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 21878176
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                lignocellulosic biomass,stress factor,stress response,target genes,robust strain construction

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