Optimization and Analysis of the Fermentation Process for Microbial Products: 2nd Edition

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Fermentation Process Design".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 3417

Special Issue Editor

Department of Bioengineering, Qilu University of Technology, Shandong Academy of Sciences, Jinan 250353, China
Interests: food biotechnology; microbial fermentation engineering; metabolic engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fermentation process optimization refers to the improvement of the production, productivity, and conversion rate of target metabolites in the fermenter through the control of operating conditions on the basis of the obtained high-yield strain. The fermentation process is usually carried out in a specific reactor. Since the microbial reaction is a self-catalytic reaction, the microbial cell itself is also a reactor, and all the substances to come out of the microreactor of the cell must pass through the boundary line between the cell and the environment, so that all reactions that occur in the cell (i.e., the biological phase) are closely linked to the environmental condition (i.e., the abiotic phase). The actual biological reaction system is a very complex three-phase system, that is, a mixture of gas, liquid, and solid phases, and the concentration gradient between the three phases varies greatly by several orders of magnitude. Therefore, to optimize such a complex system, an elaborate analysis and study of the fermentation process must be carried out. This Special Issue covers topics such as the following:

  • Improvement of the producing strains by irrationality and rationality methods;
  • Design and optimization of fermentation media;
  • The optimization and control of the fermentation process to maximize production or minimize costs;
  • Analyses of the improvement of fermentation process optimization by physiology and omics.

The aim of this Special Issue is to publish both recent innovative research results as well as review papers on the optimization and analysis of fermentation processes for microbial products.

Sincerely,

Dr. Xidong Ren
Guest Editor

Manuscript Submission Information

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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. Fermentation 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 2100 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

  • process optimization
  • integrated fermentation
  • technoeconomic analysis
  • artificial intelligence
  • artificial neural network
  • factorial designs
  • genomics
  • transcriptomics
  • proteomics
  • metabolomics

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Published Papers (3 papers)

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Research

22 pages, 1687 KiB  
Article
Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
by María Teresita Castañeda, Sebastián Nuñez, Martín Jamilis and Hernán De Battista
Fermentation 2025, 11(6), 354; https://doi.org/10.3390/fermentation11060354 - 18 Jun 2025
Viewed by 431
Abstract
Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. [...] Read more.
Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy source mass feed rate (Fin·sr) and its concentration in the feed (sr) based on lipid accumulation targets, and defined minimum feeding flow rate (Fin) according to process duration. We then assessed the impact of these parameters on commonly used bioprocess metrics—lipid yield, titer, productivity, and intracellular accumulation—across wild-type and engineered strains. Our results showed that the selection of Fin·sr was strongly strain-dependent and significantly influenced strain performance. Moreover, for a given Fin·sr, the specific values of sr, and the resulting Fin, had distinct and non-equivalent effects on performance metrics. This methodology enables the rational pre-selection of feeding strategies and strains, improving resource efficiency and reducing the probability of failed experiments. Full article
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20 pages, 3425 KiB  
Article
Enhanced L-Leucine Production in Escherichia coli via CRISPR-Associated Transposase Genome Engineering
by Xiankun Ren, Nan Li, Zhaoqi Li, Yangyi Zhou, Zerun Lin, Peng Du, Jing Xiao, Chuanzhuang Guo and Jianbin Wang
Fermentation 2025, 11(6), 314; https://doi.org/10.3390/fermentation11060314 - 1 Jun 2025
Viewed by 564
Abstract
L-leucine, an essential amino acid which cannot be synthesized in mammals, has extensive applications in various fields. However, the large-scale production of L-leucine still faces various challenges in terms of strain and process optimization. In this study, E. coli A211 was used as [...] Read more.
L-leucine, an essential amino acid which cannot be synthesized in mammals, has extensive applications in various fields. However, the large-scale production of L-leucine still faces various challenges in terms of strain and process optimization. In this study, E. coli A211 was used as the initial strain, and a double enhancement strategy of CRISPR-associated transposase genome integration and a plasmid was employed to enhance the L-leucine metabolic pathway. We constructed four engineered strains—E. coli A101, E. coli B201, E. coli CD301, and E. coli bcd401. The transcriptional levels of key genes (leuA, leuCD, leuB, and bcd) in L-leucine biosynthesis were significantly upregulated to boost L-leucine production. Fermentation screening revealed that E. coli CD301 exhibited the highest L-leucine titer (0.57 ± 0.01 g/L), presenting a 97% increase compared with the parental strain. The fermentation process of E. coli CD301 was further optimized using single-factor optimization followed by response surface methodology of variables such as temperature, C/N ratio, and inoculum size, leading to an enhanced L-leucine titer of 0.89 ± 0.03 g/L, a 56.1% improvement over the pre-optimization level. This study demonstrated the effectiveness of CRISPR-associated transposase genome integration and plasmid double enhancement strategy, providing new insights into metabolic engineering approaches for improving L-leucine production via fermentation with E. coli. Full article
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13 pages, 2186 KiB  
Article
Effect of Fermentation Duration on the Chemical Compounds of Coffea arabica from Ultra Performance Liquid Chromatography–Triple Quadrupole Mass Spectrometry and Gas Chromatography–Mass Spectrometry Analysis During the Washed Processing
by Xiaojing Shen, Qi Wang, Tingting Zheng, Biao Yuan, Zhiheng Yin, Kunyi Liu and Wenjuan Yuan
Fermentation 2024, 10(11), 560; https://doi.org/10.3390/fermentation10110560 - 31 Oct 2024
Cited by 4 | Viewed by 1553
Abstract
The washed process is one of the traditional post-harvest processes of coffee beans, which include selective harvesting, flotation, pulping, submerged fermentation underwater, washing, and drying operations. During the washed processing, fermentation underwater can remove coffee mucilage and change metabolites by microorganisms. Therefore, coffee [...] Read more.
The washed process is one of the traditional post-harvest processes of coffee beans, which include selective harvesting, flotation, pulping, submerged fermentation underwater, washing, and drying operations. During the washed processing, fermentation underwater can remove coffee mucilage and change metabolites by microorganisms. Therefore, coffee fermentation is a key factor influencing coffee’s flavor. To compare the influence of fermentation duration in an open environment of Coffea arabica in 48 h during the washed processing on the coffee’s flavor, the sensory characteristics of the coffee at different fermentation durations were evaluated using the Specialty Coffee Association of America (SCAA) cupping protocol. Moreover, ultra performance liquid chromatography–triple quadrupole mass spectrometry (UHPLC–MS/MS) and gas chromatography–mass spectrometry (GC–MS) were combined to analyze and compare the chemical compounds of coffee samples from fermentation durations of 24 h (W24) and 36 h (W36) during the washed processing method. The results showed that W36 had the highest total cupping score with 77.25 in all different fermentation duration coffee samples, and 2567 non-volatile compounds (nVCs) and 176 volatile compounds (VCs) were detected in W36 and W24 during the washed processing method. Furthermore, 43 differentially changed non-volatile compounds (DCnVCs) and 22 differentially changed volatile compounds (DCVCs) were detected in W36 vs. W24. Therefore, suitable fermentation duration in an open environment is beneficial to coffee flavor, judging by chemical compound changes. For the washed primary processing of C. arabica from Yunnan, China, 36 h fermentation was the suitable fermentation duration in an open environment, which presented potential value as the reference for washed coffee processing in the food industry. Full article
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