Stress Tolerance in Yeast Biotechnology

A Special Issue of Journal of Fungi (ISSN 2309-608X) belonging to the section "Fungi in Agriculture and Biotechnology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 6318

Editors


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Guest Editor
1. Department of Bioengineering and iBB—Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
2. Associate Laboratory i4HB—Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal
Interests: response and tolerance to stress; physiological genomics; signaling pathways; yeast diversity; advanced yeast biorefineries; yeast biotechnology
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Guest Editor
1. Centre of Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal
2. LABBELS–Associate Laboratory, Guimaraes, Portugal
Interests: industrial biotechnology; precision fermentation; metabolic engineering; bioprocess engineering; biorefineries; recombinant protein production; metabolite production

Special Issue Information

Dear Colleagues,

Yeasts are exposed to a variety of adverse environmental conditions during industrial bioprocesses. These stresses include non-optimal temperatures and pH, osmotic challenges, and the presence of inhibitory compounds, which may originate from the pre-treatment of raw materials—such as in lignocellulosic biomass hydrolysates—or accumulate during fermentation as metabolic by-products and target bioproducts. Importantly, with the growing demand for sustainable, circular production systems, there is an increasing focus on using diverse, renewable feedstocks, particularly agro-industrial residues, including not only lignocellulosic materials, but also food processing by-products and food waste. These abundant, underexploited resources represent a vital component of the present and future bioeconomy, providing an alternative to fossil resources and contributing to waste minimization and resource valorization.

However, these complex substrates introduce additional stresses and variabilities to fermentation processes, as they often contain a mixture of specific inhibitory compounds alongside fermentable nutrients. To sense, survive, and adapt to these challenging and dynamic environments, yeasts rely on complex signaling networks that coordinate global transcriptional responses and drive physiological adjustments.

Understanding these molecular mechanisms is crucial for improving yeast stress tolerance—a key factor not only in maintaining microbiological stability in foods and beverages but also in ensuring the robustness, efficiency, and economic viability of industrial bioprocesses. Yet, beyond molecular insights, it is equally important to translate this knowledge into bioprocess optimization strategies. Integrating biological understanding with bioengineering approaches—such as adaptive process control, dynamic feeding, and tailored bioprocess design—can significantly enhance process resilience and productivity, especially when dealing with the heterogeneous, inhibitor-rich nature of food and agro-industrial wastes.

The diversity of yeast species, including the well-established Saccharomyces cerevisiae and a growing range of non-conventional yeasts, offers promising solutions to tackle these challenges and broaden the range of usable substrates and bioproducts.

This Special Issue aims to provide an integrated perspective on yeast stress tolerance, bridging fundamental biological studies with applied bioprocess optimization. It will cover molecular mechanisms, systems biology approaches, strain engineering, and process design, focusing on both conventional and emerging yeast species. By emphasizing the role of agro-industrial residues, food by-products, and food waste valorization in the bioeconomy, this collection seeks to foster innovations that support resilient, flexible, and sustainable bioprocesses in industrial biotechnology for a circular, bio-based future.

Prof. Dr. Isabel Sá-Correia
Dr. Lucília Domingues
Guest Editors

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Keywords

  • response and adaptation to stress
  • stress tolerance
  • gene and genomic expression under stress
  • stress-induced signaling pathways
  • yeast diversity
  • saccharomyces and non-Saccharomyces yeasts
  • tolerance improvement
  • metabolic engineering
  • synthetic biology
  • adaptive laboratory evolution
  • strain robustness
  • multi-tolerance to stress
  • fermentation efficiency
  • bioprocess optimization
  • bioprocesses in the food and beverage industry
  • valorization of agro-industrial residues
  • bioconversion of lignocellulosic biomass
  • yeast biorefineries
  • circular bioeconomy
  • industrial biotechnology

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Published Papers (4 papers)

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Research

18 pages, 2041 KB  
Article
Tuning FLO1 Expression via Promoter Engineering Modulates Flocculation Degree and Acetic Acid Stress Tolerance in Saccharomyces cerevisiae
by Pei-Liang Ye, Wei-Bin Wang, Liang Xiong, Guang-Xian Peng, Cheng Cheng and Xin-Qing Zhao
J. Fungi 2026, 12(1), 47; https://doi.org/10.3390/jof12010047 - 9 Jan 2026
Cited by 1 | Viewed by 1084
Abstract
Robust yeast tolerance to inhibitors is essential for lignocellulosic biorefinery. Although cell flocculation is known to enhance acetic acid stress tolerance, the impact of its intensity remains unclear. In this study, engineered S. cerevisiae strains with distinct floc sizes were constructed through promoter [...] Read more.
Robust yeast tolerance to inhibitors is essential for lignocellulosic biorefinery. Although cell flocculation is known to enhance acetic acid stress tolerance, the impact of its intensity remains unclear. In this study, engineered S. cerevisiae strains with distinct floc sizes were constructed through promoter engineering. The native FLO1 promoter in the non-flocculating laboratory strain BY4741 was replaced with either the constitutive strong promoter PGK1p or the ethanol-inducible promoter TPS1p using CRISPR-Cas9-mediated genome editing, resulting in strongly and moderately flocculating strains BY4741 PGK1p-FLO1 and BY4741 TPS1p-FLO1, respectively. It was revealed that the BY4741 PGK1p-FLO1 showed a survival advantage in the late-stage fermentation and severe stress condition in the presence of 7.5 g/L acetic acid, while BY4741 TPS1p-FLO1 exhibited superior growth and fermentation performance under 5.0 g/L acetic acid stress. Further studies suggested that the enhanced acetic acid tolerance in flocculating cells was associated with their ability to maintain significantly higher intracellular ATP levels under stress. Our work highlights the importance of optimizing flocculation properties for robust industrial fermentation, and also provides a strategic basis for engineering stress-tolerant yeast strains for efficient fermentation in inhibitor-rich cellulosic hydrolysates. Full article
(This article belongs to the Special Issue Stress Tolerance in Yeast Biotechnology)
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22 pages, 3368 KB  
Article
Stress-Induced Cross-Protection and Combined Stress Responses in Extremotolerant Black Yeasts
by Klavdija Fortuna, Maja Kajin and Cene Gostinčar
J. Fungi 2026, 12(1), 43; https://doi.org/10.3390/jof12010043 - 6 Jan 2026
Cited by 1 | Viewed by 1432
Abstract
Extremotolerant fungi inhabit environments with multiple overlapping stressors, yet most studies examine stresses individually. We tested whether preconditioning with salt, cold, or both improves survival after desiccation and freezing, and whether combined salinity and temperature effects on growth are additive or synergistic. We [...] Read more.
Extremotolerant fungi inhabit environments with multiple overlapping stressors, yet most studies examine stresses individually. We tested whether preconditioning with salt, cold, or both improves survival after desiccation and freezing, and whether combined salinity and temperature effects on growth are additive or synergistic. We studied Aureobasidium pullulans, Aureobasidium subglaciale, Aureobasidium melanogenum, and Hortaea werneckii (haploid and diploid). All preconditioning treatments significantly increased long-term desiccation survival in A. pullulans, reflecting its generalist capacity to activate cross-protective responses. H. werneckii displayed smaller improvements, consistent with a specialist strategy. Freezing survival without cryoprotectants remained ~100% in both species, indicating high intrinsic tolerance. Growth analyses revealed synergistic effects of salinity and temperature in Aureobasidium spp. Species differed in salinity sensitivity (A. melanogenum > A. pullulans > A. subglaciale) and thermal preferences. A. melanogenum and A. pullulans grew faster at higher temperatures, while A. subglaciale showed the opposite trend. In H. werneckii, salinity governed growth. Haploids slowed as salinity increased, while the diploid remained unaffected. This is the first confirmation of the long-standing suggestion that hybrid diploid genomes of many H. werneckii are an adaptation to osmotic stress. These findings illustrate two pathways to extremotolerance: inducible flexibility in Aureobasidium versus constitutive halotolerance in H. werneckii. Full article
(This article belongs to the Special Issue Stress Tolerance in Yeast Biotechnology)
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17 pages, 3837 KB  
Article
Zinc-Finger 5 Is an Activation Domain in the Saccharomyces cerevisiae Stress-Responsive Transcription Factor Fzf1
by Ying Du, Wayne Y. Wang and Wei Xiao
J. Fungi 2026, 12(1), 15; https://doi.org/10.3390/jof12010015 - 25 Dec 2025
Cited by 1 | Viewed by 1544
Abstract
Fzf1 is a Saccharomyces cerevisiae transcription factor that contains five zinc finger domains (ZF1-5) and induces the expression of at least five genes in response to various chemical stresses by recognizing the shared promoter consensus sequence CS2. The N-terminal ZF1-3 are required and [...] Read more.
Fzf1 is a Saccharomyces cerevisiae transcription factor that contains five zinc finger domains (ZF1-5) and induces the expression of at least five genes in response to various chemical stresses by recognizing the shared promoter consensus sequence CS2. The N-terminal ZF1-3 are required and sufficient for binding to CS2, while ZF4 negatively regulates the activity of Fzf1. However, the effect of ZF5 on the activity of Fzf1 is not well defined. In this study, substitutions of the two zinc-coordinating Cys residues (C248S and C253S) of ZF5, or deletion of the whole ZF5 domain, compromised the chemical stress-induced activation of Fzf1. Since the elevated Fzf1-regulated gene expression caused by fzf1-ZF4 could also be reversed by additional deletion of ZF5 or C248S/C253S substitutions, fzf1-ZF5 mutations are epistatic over fzf1-ZF4 mutations. Furthermore, fzf1-ZF5 mutations are recessive to FZF1, while ZF5 is dispensable for the CS2 binding. Finally, Fzf1-ZF5 is required and sufficient to serve as a transcription activation domain when fused to a Gal4 DNA-binding domain. These observations collectively support a working model in which Fzf1 bound to its target gene promoters remains inactive due to an inhibitory activity of ZF4. Upon chemical stress, ZF4 is no longer able to inhibit the ZF5 transactivation activity, leading to the induction of Fzf1-regulated gene expression and subsequent chemical detoxification. Full article
(This article belongs to the Special Issue Stress Tolerance in Yeast Biotechnology)
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17 pages, 1622 KB  
Article
Yeast Species Associated with Industrial Cultures of the Marine Microalgae Tisochrysis lutea: Temperature Profiles and Auxin Production
by Madalena Matos, Mónica A. Fernandes, Natacha Coelho, Tamára F. Santos, João Varela, Alexandre M. C. Rodrigues and Isabel Sá-Correia
J. Fungi 2025, 11(11), 818; https://doi.org/10.3390/jof11110818 - 18 Nov 2025
Cited by 4 | Viewed by 1597
Abstract
This study provides the first systematic characterization of culturable yeast diversity associated with large-scale cultivation of Tisochrysis lutea. This marine haptophyte is widely used in aquaculture for its high content of essential fatty acids, pigments, and other bioactive compounds. Culture sampling was [...] Read more.
This study provides the first systematic characterization of culturable yeast diversity associated with large-scale cultivation of Tisochrysis lutea. This marine haptophyte is widely used in aquaculture for its high content of essential fatty acids, pigments, and other bioactive compounds. Culture sampling was conducted at Necton S.A. facilities (Olhão, Portugal) over full production cycles from 5 L flasks until tubular photobioreactors during the months of May and June. The study aimed to identify and isolate the present yeast species and evaluate their physiological traits relevant to potential co-cultivation strategies. All retained isolates belonged to the phylum Basidiomycota, with six species identified: Rhodotorula sphaerocarpa (45%), R. mucilaginosa (20%), R. diobovata (13%), Vishniacozyma carnescens (16%), Naganishia diffluens (3%), and Moesziomyces aphidis (3%). Temperature growth profiles (10–40 °C), tolerance to artificial sea water, and auxin production were characterized, revealing that, except for V. carnescens, the yeast isolates grow optimally at 25–30 °C, within the ideal range for T. lutea cultivation. Results suggest that some of these marine yeasts, particularly R. sphaerocarpa and R. mucilaginosa isolates, could serve as biological enhancers of algal productivity, in situ. This foundational work supports future efforts to develop targeted yeast management or co-cultivation strategies, with the goal of improving biomass yield and metabolite production in industrial T. lutea photobioreactors. Full article
(This article belongs to the Special Issue Stress Tolerance in Yeast Biotechnology)
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