Recent Advances in the Production of Pharmaceuticals through Fermentation

A special issue of Fermentation (ISSN 2311-5637). This special issue belongs to the section "Microbial Metabolism, Physiology & Genetics".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 5867

Special Issue Editors


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Guest Editor
School of Pharmacy, Shanghai Jiaotong University, Shanghai, China
Interests: fermentation process optimization; strain improvement; metabolic engineering of microorganisms; separation and purification

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Guest Editor
School of Biotechnology, East China University of Science and Technology, Shanghai, China
Interests: microbial physiology; metabolic engineering of microorganisms; fermentation process optimization and up-scaling

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Guest Editor
School of Biotechnology, East China University of Science and Technology, Shanghai, China
Interests: bioprocess engineering; high-throughput screening; metabolic engineering of microorganisms

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Guest Editor Assistant
School of Pharmacy, Shanghai Jiaotong University, Shanghai, China
Interests: fermentation; biotransformation; antibiotics; probiotics; natural products

Special Issue Information

Dear Colleagues,

Drug discovery and large-scale manufacturing through fermentation, represented by traditional small  molecules of antibiotics and modern macromolecules of antibodies, have significantly increased the average lifespan of humans. The low-cost and high-quality production of such drugs requires improvements in various aspects, such as drug producers, fermentation, purification, and quality control, which is the eternal focus of pharmaceutical companies and the mission of the academic community.

The Special Issue will present  recent advances in the pharmaceutical industry and academic community through fermentation, especially the construction of high-yield and high-quality producers using synthetic biology technology, the optimization and scaling up of fermentation processes based on multi-scale regulation methodologies with the aid of advanced sensor technology, and the efficient purification of products using systematical separation engineering technology. This Special Issue also welcomes comprehensive forward-looking review papers on frontier research and industry developments in pharmaceutics.

Prof. Dr. Daijie Chen
Prof. Dr. Ju Chu
Dr. Xiwei Tian
Guest Editors

Dr. Shidong Kan
Guest Editor Assistant

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. 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

  • drug biosynthesis and innovative drug discovery
  • drug synthetic biology and drug producer screening
  • new technologies for drug fermentation, separation and purification
  • new technologies for drug engineering production and efficient manufacturing
  • novel fermentation regulation strategy in the context of synthetic biology
  • prospects for pharmaceutical research and industry development
  • new technologies for large scale production

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Published Papers (2 papers)

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Research

13 pages, 2075 KiB  
Article
Optimization of the Process of Chinese Hamster Ovary (CHO) Cell Fed-Batch Culture to Stabilize Monoclonal Antibody Production and Overall Quality: Effect of pH Control Strategies
by Kexue Liang, Hongzhen Luo and Qi Li
Fermentation 2024, 10(7), 352; https://doi.org/10.3390/fermentation10070352 - 12 Jul 2024
Viewed by 3126
Abstract
Monoclonal antibodies (mAbs) used in biomedical research and therapeutic applications are primarily produced by Chinese hamster ovary (CHO) cells via fed-batch culture. The growing need for elevated quantities of biologics mandates the continual optimization of the mAb production process. The development of an [...] Read more.
Monoclonal antibodies (mAbs) used in biomedical research and therapeutic applications are primarily produced by Chinese hamster ovary (CHO) cells via fed-batch culture. The growing need for elevated quantities of biologics mandates the continual optimization of the mAb production process. The development of an effective process control method is indispensable for the production of specified mAbs by CHO cells. In this study, the effects of the pH control strategy on CHO cell fed-batch culture to produce an antibody (EA5) were first investigated in a 3 L bioreactor. The results indicate that controlling the culture pH at 7.2 during the fed-batch stage could produce a higher EA5 titer of 6.1 g/L with a lower Man5 ratio of 2.2% by day 14. Based on this, an optimized CHO cell fed-batch culture was conducted in a 15 L bioreactor to verify its effectiveness and stability. In this case, on day 14, an EA5 titer of 6.5 g/L was achieved with productivity of 0.46 g/L/day, which was 1.07-fold higher compared to that of the culture in the 3 L bioreactor. Furthermore, regarding the product quality, a monomer abundance of 96.0%, a main peak of 55.0%, and a Man5 proportion of 2.4% were maintained in the 15 L bioreactor. In addition, different cell clarification processes were evaluated using the CHO cell culture broth from the 3 L and 15 L bioreactors to further improve productivity and economic performance. Overall, this study provides some directions for process intensification and improving the quality of mAbs produced by CHO cells in the biopharmaceutical industry. Full article
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19 pages, 13322 KiB  
Article
Proteomic Analysis of the Effect of CaCl2 and Sodium Citrate on Gentamicin Biosynthesis of Micromonospora echinospora SIPI-GM.01
by Ping Yang, Huimin Lin, Xiaowei Wu, Yu Yin, Ji’an Li and Daijie Chen
Fermentation 2023, 9(12), 997; https://doi.org/10.3390/fermentation9120997 - 23 Nov 2023
Viewed by 1818
Abstract
The clinical antibiotic gentamicin is a mixture of several difficult-to-separate components, the minor group of which is gentamicin C1a, a precursor for the synthesis of the high-efficacy and low-toxicity antibiotic etimicin. This study aimed to achieve the high production of gentamicin as well [...] Read more.
The clinical antibiotic gentamicin is a mixture of several difficult-to-separate components, the minor group of which is gentamicin C1a, a precursor for the synthesis of the high-efficacy and low-toxicity antibiotic etimicin. This study aimed to achieve the high production of gentamicin as well as gentamicin C1a. In this study, the influence of organic and inorganic salts on the gentamicin production was screened and label-free proteomics was used to determine the mechanisms responsible for the effects. In 25 L fermentation experiments, the addition of 0.1% CaCl2 and 0.3% sodium citrate increased gentamicin titers by 11.5% (2398 μg/mL vs. 2150 μg/mL), while the C1a ratio increased from 38% to 42%. The results showed that CaCl2 downregulated the synthesis and metabolism of the tetrapyrrole pathway and the GenK protein (0.08-fold) in the gentamicin synthesis pathway, whereas sodium citrate downregulated key proteins in the glycosylation pathway and tricarboxylic acid pathway. Thus, CaCl2 caused changes in methylation during the synthesis of gentamicin, increasing the proportion of gentamicin C1a. In contrast, sodium citrate inhibited primary metabolism to promote the production of secondary metabolites of gentamicin. This study provided a basis for the co-production of gentamicin C1a mono-component and gentamicin multicomponent. Full article
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