Systems Metabolic Engineering for the Production of Value-Added Compounds

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

Deadline for manuscript submissions: closed (20 February 2026) | Viewed by 3148

Special Issue Editors


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Guest Editor
School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Interests: heterologous biosynthesis; bioproducts; natural products; genetic engineering; metabolic engineering; bioprocess
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
Interests: heterologous biosynthesis; bioproducts; natural products; genetic engineering; metabolic engineering; bioprocess
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Microorganisms play a vital role in modern life. Over the past decade, research into microbial fermentation for producing value-added compounds with nutritional, pharmaceutical and biofuel properties has grown increasingly sophisticated and widespread.  The advances in genome sequencing and editing techniques together with synthetic biology tools have enabled researchers to identify the regulatory mechanisms underlying the overproduction of secondary metabolites and to monitor gene expression during the fermentation cycle, accelerating the rational application of metabolic pathway engineering.

For this Special Issue, we invite leading researchers and authors to submit their original research and review articles exploring the production of those value-added compounds from genetically engineered microbial strains (including Escherichia coli and Bacillus subtilis, Saccharomyces cerevisiae and Pichia pastoris, Streptomyces coelicolor and Streptomyces lividans, Aspergillus nidulans and Aspergillus oryzae, etc.). Papers focused on efforts to improve microbial strains and that address the complex problems of screening, advanced tools, and technology used for metabolic pathway rebuilding and fine-tuning, and new strategies for process optimization, are especially welcome to be submitted.

We particularly welcome submissions focused on:

  • Strategies for microbial strain improvement and addressing complex challenges in screening;
  • Advanced tools and technologies for metabolic pathway rebuilding and fine-tuning;
  • Novel strategies for process optimization;
  • Purification and Characterization of Metabolites

Dr. Guojian Zhang
Prof. Dr. Fu Yan
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 250 words) can be sent to the Editorial Office for assessment.

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

  • heterologous biosynthesis
  • bioproducts
  • natural products
  • genetic engineering
  • metabolic engineering
  • bioprocess

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Published Papers (2 papers)

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Research

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16 pages, 2343 KB  
Article
One-Step Activation, Purification, and Immobilization of Bovine Chymosin via Adsorption on Magnetic Particles
by Paulina G. Gonçalves, Paz García-García, Honoria S. Chipaca-Domingos, Gloria Fernandez-Lorente, Miguel Ladero and Benevides C. Pessela
Fermentation 2026, 12(1), 66; https://doi.org/10.3390/fermentation12010066 - 22 Jan 2026
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Abstract
Chymosin is an aspartyl protease widely used in the food industry for milk coagulation during cheesemaking. Although recombinant production has replaced natural extraction from rennet, current heterologous expression systems still face significant challenges, including low solubility, costly purification steps, and enzyme instability after [...] Read more.
Chymosin is an aspartyl protease widely used in the food industry for milk coagulation during cheesemaking. Although recombinant production has replaced natural extraction from rennet, current heterologous expression systems still face significant challenges, including low solubility, costly purification steps, and enzyme instability after activation. To address these limitations, we sought to develop a more efficient and economical production strategy for bovine chymosin by cloning its codon-optimized prochymosin A gene into Escherichia coli using the pBAD/His vector under the control of the L-arabinose-inducible PBAD promoter. Overexpression of the recombinant gene resulted in the formation of inclusion bodies, which were solubilized with NaOH and refolded by dilution and pH adjustment with glycine. The folded prochymosin was then activated by acidification. To simplify the downstream process and improve enzyme recovery, different immobilization strategies were explored to combine activation, purification, and immobilization in a single step. While polymeric agarose-based supports showed low immobilization efficiency (<20%) due to pore clogging, magnetic nanoparticles completely overcame these limitations, achieving nearly 100% immobilization yield and retaining about 85% of enzymatic activity. This integrated magnetic-based approach provides a cost-effective and scalable alternative for the production and stabilization of active chymosin. Full article
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Review

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29 pages, 709 KB  
Review
Bacterial Extracellular Vesicles in Biotechnology: Current Challenges and Strategies for Production Enhancement
by Flavia Cannizzaro, Annamaria Gallo, Silvia La Scala, Giuseppe Gallo and Teresa Faddetta
Fermentation 2026, 12(2), 86; https://doi.org/10.3390/fermentation12020086 - 3 Feb 2026
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Abstract
Bacterial extracellular vesicles (BEVs) are nanosized (10–400 nm), membrane-enclosed particles naturally secreted by both Gram-negative and Gram-positive bacteria. Initially characterized as virulence factors in pathogenic species, BEVs are now recognized as multifunctional entities with significant biotechnological potential. Their cargo—comprising proteins, lipids, nucleic acids, [...] Read more.
Bacterial extracellular vesicles (BEVs) are nanosized (10–400 nm), membrane-enclosed particles naturally secreted by both Gram-negative and Gram-positive bacteria. Initially characterized as virulence factors in pathogenic species, BEVs are now recognized as multifunctional entities with significant biotechnological potential. Their cargo—comprising proteins, lipids, nucleic acids, and metabolites—enables diverse biological activities, including immune modulation, epithelial barrier protection, stress tolerance, and intercellular communication. Recent studies have highlighted BEVs from biotechnologically relevant bacteria—such as plant growth-promoting rhizobacteria, lactic acid bacteria, bifidobacteria, cyanobacteria, bacilli, and streptomycetes—for their different roles in biological and ecological interactions. These properties underpin emerging applications in health, agriculture, and bioprocessing, including next-generation postbiotics, vaccine platforms, drug and RNA delivery systems, and novel plant biostimulants. However, major challenges persist, particularly low production yields, variability in cargo composition, and scalability. Addressing these limitations requires a deeper understanding of vesiculation mechanisms and the development of process-oriented strategies for BEV recovery and purification. This review synthesizes recent advances in genetic analysis, physiological modulation, physicochemical stimuli, and bioprocess optimization aimed at enhancing BEV production and stabilizing cargo profiles, providing a comprehensive overview of approaches to unlock the full potential of BEVs as versatile biotechnological tools. Full article
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