Microbial Metabolism Regulation in Engineered Production Strains

Dear Colleagues,

Redefining microbial metabolism and controlling it represent key challenges in developing modified strains for industrial biotechnology. Genetic modifications can establish new biosynthetic pathways or enhance existing ones; however, cellular metabolism is strictly regulated by networks that have evolved to prioritize growth and survival over product synthesis. Consequently, these genetically modified strains must choose between growth and production, which at the industrial level can mean the difference between a profitable strain and one that is discarded. However, redirecting carbon flow toward a specific product also imposes a metabolic burden, which can reduce cellular fitness, leading to instability over time.

Therefore, regulation of microbial metabolism represents another main challenge in creating modified production strains for industrial biotechnology. While genetic modifications can establish new biosynthetic pathways or improve existing ones, cellular metabolism is strictly regulated by networks that have evolved to prioritize growth and survival over product synthesis. Consequently, effectively biotechnologically modified strains require both the creation of new pathways and a meticulous reconfiguration of existing regulatory mechanisms.

At the transcriptional level, global control mechanisms such as catabolic repression favor the preferential use of substrates, thereby inhibiting alternative metabolic pathways and limiting the effective utilization of complex raw materials. Moreover, a similar effect could be observed with other global transcription factors in the regulation of metabolic fluxes according to nitrogen sources, phosphorus or sulfur concentrations, or the oxygen response. Simultaneously, metabolic flux is limited by enzymatic capacity, thermodynamic principles, and the availability of essential cofactors such as NADH, NADPH, and ATP. These cofactors act as essential regulatory points, linking redox balance and energy status to pathway functionality. Imbalances in cofactor levels often decrease yields or lead to the accumulation of unwanted intermediates.

Considering that, redirecting carbon flux toward a specific product imposes a metabolic burden and can reduce cellular fitness, leading to instability over time. Furthermore, static overexpression of enzymes in the pathway often causes bottlenecks due to uneven flux distribution.

In sum, the regulation of microbial metabolism in biotechnological processes is a systems-level challenge that requires the synchronized management of gene expression, enzymatic activity, and cellular resources to achieve efficient and consistent production.

All these challenges constitute the core of this Special Issue applied to different microbial products (antibiotics, carotenoids, immunosuppressants, steroids, and others), pathways (new pathways through synthetic biology strategies, widening and optimizing metabolic fluxes, etc.), or processes (biocatalysis, food and feed production and preservation, plastics degradation, biofuels, and others).

Prof. Dr. José María Luengo
Dr. Elias R. Olivera
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. Microorganisms 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 2700 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.

• systems metabolic engineering
• metabolic flux control
• gene expression tuning
• biotechnological chassis
• pathway optimization
• synthetic biology
• carbon catabolite repression
• cofactor balance
• redox homeostasis