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New Trends in Yeast Metabolic Engineering
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New Trends in Yeast Metabolic Engineering

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: 31 May 2024 | Viewed by 5096

Special Issue Editors

Prof. Dr. Aiqun Yu

E-Mail Website
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

E-Mail Website
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

E-Mail Website
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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Published Papers (5 papers)

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Research

19 pages, 6804 KiB  
Article
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 151
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 [...] Read more.
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)
13 pages, 2907 KiB  
Article
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
Viewed by 962
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 [...] Read more.
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  
Article
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
Viewed by 1003
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 [...] Read more.
(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  
Article
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
Viewed by 1122
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 [...] Read more.
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  
Article
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 - 09 Dec 2023
Viewed by 984
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 [...] Read more.
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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