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A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungi in Agriculture and Biotechnology".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 16551

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Prof. Dr. Aiqun Yu

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Guest Editor

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No. 29 the 13th Street TEDA, Tianjin 300457, China
Interests: metabolic engineering; pathway engineering; engineered yeast; biochemical production; biosynthesis

Dr. Jiwei Mao

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Guest Editor

Department of Life Sciences, Chalmers University of Technology, SE412 96 Gothenburg, Sweden
Interests: synthetic biology; medical biotechnology; microbial cell factories; natural products; artificial foods; whole-cell biosensors; Saccharomyces cerevisiae; biocatalysis

Dr. Ning Xu

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Guest Editor

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China
Interests: physiological engineering; microbial robustness; synthetic biology; genome editing; biomanufacturing

Special Issue Information

Dear Colleagues,

To mitigate the effects of climate change, environmental pollution, population growth, and the sharp decline in agricultural land, the development of microbial cell factories has emerged as a commercially attractive hotspot for highly efficiently producing different chemicals due to the green, cost-competitive and sustainable advantages. Yeast, as a unicellular eukaryote, has long been exploited for industrial and biotechnological applications and is extensively chosen as the starting platform for valuable metabolite biosynthesis and production in the emerging field of synthetic biology and metabolic engineering. Nowadays, with the help of state-of-the-art synthetic and systems biology technologies, yeast cells are widely used to solve a variety of societal challenges in the environment, energy and health. Therefore, the Journal of Fungi has decided to open a Special Issue on “New Trends in Yeast Metabolic Engineering”.

This Special Issue is primarily intended to collect research articles and reviews. We particularly welcome articles on, but not limited to, the following topics:

Engineering yeast cell factories for the production of native and non-native metabolites and chemicals, including but not limited to natural products, industrial enzymes, artificial foods, biofuels, biomaterials, biopolymers, biosurfactants, bioemulsifiers, biopigments, food ingredients, agrochemicals, nutraceuticals, and pharmaceuticals;
Bioconversion of agricultural, food processing and forestry wastes into value-added products using yeast systems;
Development of yeasts for therapeutic application and advanced drug discovery platforms;
Metabolic rewiring of yeasts for enhanced conversion of one-carbon (C1) compounds into high-value chemicals;
Exploring physiological, biochemical, and molecular mechanisms underlying stress responses in yeasts, and improving cellular robustness and fitness of chassis cells in fungal biotechnology and pathogenesis;
Innovative tools and strategies for designing and optimizing cell factories in model yeasts and non-conventional yeasts, including but not limited to biosensors, genome editing, pathway reconstruction, dynamic regulation, enzyme engineering, directed evolution and high-throughput screening;
Construction and application of genome-scale metabolic models or development of novel machine-learning approaches to devise rational design of yeast cell factories, investigate metabolic basis for human disease and fill the gaps of fundamental studies on metabolism.

Prof. Dr. Aiqun Yu
Dr. Jiwei Mao
Dr. Ning Xu
Guest Editors

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Keywords

synthetic biology
metabolic engineering
yeast
microbial cell factory
biosynthetic pathway
bioproduction
genetic editing tools
strain development
natural products
high-value chemicals

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Published Papers (9 papers)

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Research

10 pages, 3191 KiB

Open AccessArticle

Calcium-Induced Regulation of Sanghuangporus baumii Growth and the Biosynthesis of Its Triterpenoids

by Zengcai Liu, Ying Yu, Shiyuan Wang and Li Zou

J. Fungi 2025, 11(3), 238; https://doi.org/10.3390/jof11030238 - 20 Mar 2025

Viewed by 370

Abstract

Sanghuangporus baumii, a fungus used in traditional Chinese medicine, produces important pharmacological compounds such as triterpenoids, but at levels significantly lower than those required for medical use. This study investigated the effects of various concentrations of Ca²⁺ on S. baumii mycelial growth and the heterologous biosynthesis of S. baumii triterpenoids. Under induction by 10 mM Ca²⁺, the growth rate (0.39 cm/d) and biomass (4.48 g/L) of S. baumii mycelia were 1.03% and 10.05% higher than those in the 0 mM Ca²⁺-treatment group, respectively. In contrast, 200 mM Ca²⁺ significantly inhibited the growth rate and biomass of the mycelia. Notably, the total triterpenoid content reached its peak (17.71 mg/g) in the 200 mM Ca²⁺-treatment group, with a significant increase in the Ca²⁺ content (3869.97 µg/g) in the mycelia. Subsequently, the differential metabolic pathways and related genes between the S. baumii groups were examined using transcriptomic analysis. The results indicated that the increase in the growth rate and biomass of S. baumii mycelia was primarily due to elevated soluble sugar content, whereas the growth inhibition was associated with the toxic effects of H₂O₂. The observed differences in triterpenoid content were mainly attributed to the activation of the terpenoid backbone biosynthesis pathway and the AACT gene. Finally, the AACT gene was cloned and transformed into yeast cells, thus creating strain Sc-AA1. Upon treatment at the optimal Ca²⁺ concentration, the squalene content of strain Sc-AA1 reached 0.78 mg/g, 2.89-fold higher than that in the control group. These findings are significant for the heterologous biosynthesis of triterpenoids from S. baumii. Our study demonstrates the feasibility of producing triterpenoids in Saccharomyces cerevisiae and provides a foundation for future optimization toward achieving industrially relevant yields. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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31 pages, 4000 KiB

Open AccessArticle

Assessment of Recombinant β-Propeller Phytase of the Bacillus Species Expressed Intracellularly in Yarrowia lipolityca

by Liliya G. Maloshenok, Yulia S. Panina, Sergey A. Bruskin, Victoria V. Zherdeva, Natalya N. Gessler, Alena V. Rozumiy, Egor V. Antonov, Yulia I. Deryabina and Elena P. Isakova

J. Fungi 2025, 11(3), 186; https://doi.org/10.3390/jof11030186 - 26 Feb 2025

Viewed by 485

Abstract

Phytases of the PhyD class according to their pH optimum (7.0–7.8) and high thermal stability can claim to be used in the production of feed supplements. However, today they have no practical application in feed production because there are no suitable producers sufficient for its biotechnological production compared to the PhyA and PhyC class ones. Moreover, in most cases, the technologies with the enzymes produced in secretory form are preferable for the production of phytases, though upon microencapsulation in yeast-producing cells, the phytase thermal stability increases significantly compared to the extracellular form, which improves its compatibility with spray drying technology. In this study, we assayed the intracellular heterologous expression of PhyD phytase from Bacillus species in the Yarrowia lipolytica yeast cells. While the technology has been successfully used to synthesize PhyC phytase from Obesumbacterium proteus, PhyD phytase tends to aggregate upon intracellular accumulation. Furthermore, we evaluated the prospects for the production of encapsulated phytase of the PhyD class of high enzymatic activity when it accumulates in the cell cytoplasm of the Y. lipolytica extremophile yeast, a highly effective platform for the production of recombinant proteins. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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13 pages, 1771 KiB

Open AccessArticle

Denovo Production of Resveratrol by Engineered Rice Wine Strain Saccharomyces cerevisiae HJ08 and Its Application in Rice Wine Brewing

by Huihui An, Guangpeng Li, Zhihan Yang, Meng Xiong, Na Wang, Xitao Cao and Aiqun Yu

J. Fungi 2024, 10(8), 513; https://doi.org/10.3390/jof10080513 - 23 Jul 2024

Viewed by 1558

Abstract

Resveratrol is a plant-derived polyphenolic compound with numerous biological activities and health-promoting properties. Rice wine is a popular traditional alcoholic beverage made from fermented rice grains, and widely consumed in Asia. To develop resveratrol-enriched rice wine, a heterologous resveratrol biosynthesis pathway was established by integrating the 4-coumaroyl-CoA ligase (Pc4CL) and the stilbene synthase (VvSTS) from Petroselinum crispum and Vitis vinifera at the δ locus sites of industrial rice wine strains Saccharomyces cerevisiae HJ. The resulting S. cerevisiae HJ01 produced a level of 0.6 ± 0.01 mg/L resveratrol. Next, the resveratrol production was increased 16.25-fold through employing the fused protein Pc4CL::VvSTS with a rigidly linked peptide (TPTP, EAAAK). Then, the strains were further modified by removing feedback inhibition of tyrosine through point mutation of ARO4 and ARO7, which integrated at the rDNA region of strain HJ03, and generated strain HJ06, HJ07, and HJ08. Subsequently, the highest resveratrol titer (34.22 ± 3.62 mg/L) was obtained by optimizing fermentation time and precursor addition amount. Finally, resveratrol content of rice wine fermented with strain HJ08 was 2.04 ± 0.08 mg/L and 1.45 ± 0.06 mg/L with or without the addition of 400 mg/L tyrosine after 7 days fermentation. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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22 pages, 3319 KiB

Open AccessArticle

DNA Damage Checkpoints Govern Global Gene Transcription and Exhibit Species-Specific Regulation on HOF1 in Candida albicans

by Yan Zhang, Huaxin Cai, Runlu Chen and Jinrong Feng

J. Fungi 2024, 10(6), 387; https://doi.org/10.3390/jof10060387 - 29 May 2024

Viewed by 1223

Abstract

DNA damage checkpoints are essential for coordinating cell cycle arrest and gene transcription during DNA damage response. Exploring the targets of checkpoint kinases in Saccharomyces cerevisiae and other fungi has expanded our comprehension of the downstream pathways involved in DNA damage response. While the function of checkpoint kinases, specifically Rad53, is well documented in the fungal pathogen Candida albicans, their targets remain poorly understood. In this study, we explored the impact of deleting RAD53 on the global transcription profiles and observed alterations in genes associated with ribosome biogenesis, DNA replication, and cell cycle. However, the deletion of RAD53 only affected a limited number of known DNA damage-responsive genes, including MRV6 and HMX1. Unlike S. cerevisiae, the downregulation of HOF1 transcription in C. albicans under the influence of Methyl Methanesulfonate (MMS) did not depend on Dun1 but still relied on Rad53 and Rad9. In addition, the transcription factor Mcm1 was identified as a regulator of HOF1 transcription, with evidence of dynamic binding to its promoter region; however, this dynamic binding was interrupted following the deletion of RAD53. Furthermore, Rad53 was observed to directly interact with the promoter region of HOF1, thus suggesting a potential role in governing its transcription. Overall, checkpoints regulate global gene transcription in C. albicans and show species-specific regulation on HOF1; these discoveries improve our understanding of the signaling pathway related to checkpoints in this pathogen. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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17 pages, 4506 KiB

Open AccessArticle

Integrated Transcriptomics and Metabolomics Analysis Reveal the Regulatory Mechanisms Underlying Sodium Butyrate-Induced Carotenoid Biosynthesis in Rhodotorula glutinis

by Xingyu Huang, Jingdie Fan, Caina Guo, Yuan Chen, Jingwen Qiu and Qi Zhang

J. Fungi 2024, 10(5), 320; https://doi.org/10.3390/jof10050320 - 27 Apr 2024

Viewed by 1723

Abstract

Sodium butyrate (SB) is a histone deacetylase inhibitor that can induce changes in gene expression and secondary metabolite titers by inhibiting histone deacetylation. Our preliminary analysis also indicated that SB significantly enhanced the biosynthesis of carotenoids in the Rhodotorula glutinis strain YM25079, although the underlying regulatory mechanisms remained unclear. Based on an integrated analysis of transcriptomics and metabolomics, this study revealed changes in cell membrane stability, DNA and protein methylation levels, amino acid metabolism, and oxidative stress in the strain YM25079 under SB exposure. Among them, the upregulation of oxidative stress may be a contributing factor for the increase in carotenoid biosynthesis, subsequently enhancing the strain resistance to oxidative stress and maintaining the membrane fluidity and function for normal cell growth. To summarize, our results showed that SB promoted carotenoid synthesis in the Rhodotorula glutinis strain YM25079 and increased the levels of the key metabolites and regulators involved in the stress response of yeast cells. Additionally, epigenetic modifiers were applied to produce fungal carotenoid, providing a novel and promising strategy for the biosynthesis of yeast-based carotenoids. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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13 pages, 2907 KiB

Open AccessArticle

Systematic Engineering of Saccharomyces cerevisiae for the De Novo Biosynthesis of Genistein and Glycosylation Derivatives

by Yongtong Wang, Zhiqiang Xiao, Siqi Zhang, Xinjia Tan, Yifei Zhao, Juan Liu, Ning Jiang and Yang Shan

J. Fungi 2024, 10(3), 176; https://doi.org/10.3390/jof10030176 - 26 Feb 2024

Cited by 4 | Viewed by 2646

Abstract

Isoflavones are predominantly found in legumes and play roles in plant defense and prevention of estrogen-related diseases. Genistein is an important isoflavone backbone with various biological activities. In this paper, we describe how a cell factory that can de novo synthesize genistein was constructed in Saccharomyces cerevisiae. Different combinations of isoflavone synthase, cytochrome P450 reductase, and 2-hydroxyisoflavone dehydratase were tested, followed by pathway multicopy integration, to stably de novo synthesize genistein. The catalytic activity of isoflavone synthase was enhanced by heme supply and an increased intracellular NADPH/NADP⁺ ratio. Redistribution of the malonyl-CoA flow and balance of metabolic fluxes were achieved by adjusting the fatty acid synthesis pathway, yielding 23.33 mg/L genistein. Finally, isoflavone glycosyltransferases were introduced into S. cerevisiae, and the optimized strain produced 15.80 mg/L of genistin or 10.03 mg/L of genistein-8-C-glucoside. This is the first de novo synthesis of genistein-8-C-glucoside in S. cerevisiae, which is advantageous for the green industrial production of isoflavone compounds. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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12 pages, 3845 KiB

Open AccessArticle

Systems Metabolic Engineering of Saccharomyces cerevisiae for the High-Level Production of (2S)-Eriodictyol

by Siqi Zhang, Juan Liu, Zhiqiang Xiao, Xinjia Tan, Yongtong Wang, Yifei Zhao, Ning Jiang and Yang Shan

J. Fungi 2024, 10(2), 119; https://doi.org/10.3390/jof10020119 - 31 Jan 2024

Cited by 4 | Viewed by 2498

Abstract

(2S)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered Saccharomyces cerevisiae by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of p-coumaric acid in S. cerevisiae and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2S)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the ThF3′H gene from Tricyrtis hirta. Finally, by multiplying the copy number of the ThF3′H gene, the production of ERD was further increased, reaching 132.08 mg L⁻¹. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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15 pages, 3548 KiB

Open AccessArticle

The Endoplasmic Reticulum–Plasma Membrane Tethering Protein Ice2 Controls Lipid Droplet Size via the Regulation of Phosphatidylcholine in Candida albicans

by Ying Deng, Hangqi Zhu, Yanting Wang, Yixuan Dong, Jiawen Du, Qilin Yu and Mingchun Li

J. Fungi 2024, 10(1), 87; https://doi.org/10.3390/jof10010087 - 22 Jan 2024

Cited by 1 | Viewed by 2291

Abstract

Lipid droplets (LDs) are intracellular organelles that play important roles in cellular lipid metabolism; they change their sizes and numbers in response to both intracellular and extracellular signals. Changes in LD size reflect lipid synthesis and degradation and affect many cellular activities, including energy supply and membrane synthesis. Here, we focused on the function of the endoplasmic reticulum–plasma membrane tethering protein Ice2 in LD dynamics in the fungal pathogen Candida albicans (C. albicans). Nile red staining and size quantification showed that the LD size increased in the ice2Δ/Δ mutant, indicating the critical role of Ice2 in the regulation of LD dynamics. A lipid content analysis further demonstrated that the mutant had lower phosphatidylcholine levels. As revealed with GFP labeling and fluorescence microscopy, the methyltransferase Cho2, which is involved in phosphatidylcholine synthesis, had poorer localization in the plasma membrane in the mutant than in the wild-type strain. Interestingly, the addition of the phosphatidylcholine precursor choline led to the recovery of normal-sized LDs in the mutant. These results indicated that Ice2 regulates LD size by controlling intracellular phosphatidylcholine levels and that endoplasmic reticulum–plasma membrane tethering proteins play a role in lipid metabolism regulation in C. albicans. This study provides significant findings for further investigation of the lipid metabolism in fungi. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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20 pages, 10767 KiB

Open AccessArticle

Mec1-Rad53 Signaling Regulates DNA Damage-Induced Autophagy and Pathogenicity in Candida albicans

by Jiawen Du, Yixuan Dong, Wenjie Zuo, Ying Deng, Hangqi Zhu, Qilin Yu and Mingchun Li

J. Fungi 2023, 9(12), 1181; https://doi.org/10.3390/jof9121181 - 9 Dec 2023

Cited by 2 | Viewed by 1893

Abstract

DNA damage activates the DNA damage response and autophagy in C. albicans; however, the relationship between the DNA damage response and DNA damage-induced autophagy in C. albicans remains unclear. Mec1-Rad53 signaling is a critical pathway in the DNA damage response, but its role in DNA damage-induced autophagy and pathogenicity in C. albicans remains to be further explored. In this study, we compared the function of autophagy-related (Atg) proteins in DNA damage-induced autophagy and traditional macroautophagy and explored the role of Mec1-Rad53 signaling in regulating DNA damage-induced autophagy and pathogenicity. We found that core Atg proteins are required for these two types of autophagy, while the function of Atg17 is slightly different. Our results showed that Mec1-Rad53 signaling specifically regulates DNA damage-induced autophagy but has no effect on macroautophagy. The recruitment of Atg1 and Atg13 to phagophore assembly sites (PAS) was significantly inhibited in the mec1Δ/Δ and rad53Δ/Δ strains. The formation of autophagic bodies was obviously affected in the mec1Δ/Δ and rad53Δ/Δ strains. We found that DNA damage does not induce mitophagy and ER autophagy. We also identified two regulators of DNA damage-induced autophagy, Psp2 and Dcp2, which regulate DNA damage-induced autophagy by affecting the protein levels of Atg1, Atg13, Mec1, and Rad53. The deletion of Mec1 or Rad53 significantly reduces the ability of C. albicans to systematically infect mice and colonize the kidneys, and it makes C. albicans more susceptible to being killed by macrophages. Full article

(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)

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