Strategies for Microbial Bioprocess Optimization

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Biochemical Engineering".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 1744

Editors


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Guest Editor
Department of Bioenegnieering, Imperial College London, London SW7 2AZ, UK
Interests: metabolic engineering; fermentation; synthetic biology; bioreactor design; synthetic microbial communities; biomass; renewable substrates
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Co-Guest Editor
Department of Chemical Engineering, University of Bath, Laverton Down, Bath BA2 7AY, UK
Interests: fermentation; food sustainability; bioprocessing; bioactive compounds; starter cultures
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue particularly welcomes reviews and original research papers that explore the use of metabolic engineering for the bioproduction of value-added compounds, biofuels, or bio-energy using renewable feedstocks and waste streams. Themes to be addressed may include but are not limited to the following areas:

-Strain engineering for efficient utilization of diverse feedstocks, including C1 substrates, agro-industrial feedstocks, and waste streams.

-Adaptive laboratory evolution.

-Application of metabolic modeling approaches, such as kinetic modeling or genome-scale metabolic modeling, to optimize substrate utilization.

-Machine-learning based methods to enhance carbon utilization and bioprocess optimization.

-Synthetic and natural microbial communities.

-Life cycle assessment and techno-economic analysis to evaluate the environmental and economic sustainability of engineered microbial systems.

Dr. Razieh Rafieenia
Dr. Sajad Shokri
Guest Editors

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Keywords

  • metabolic engineering
  • fermentation
  • synthetic biology
  • bioreactor design
  • synthetic microbial communities
  • machine learning based process design
  • renewable substrates
  • life cycle assessment

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Published Papers (2 papers)

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Research

39 pages, 6742 KB  
Article
Dynamic Pareto Optimization of Consolidated Bioprocessing for Ethanol Titer, Productivity, Conversion, and Operating Severity
by Mark Korang Yeboah, Nana Yaw Asiedu and Ahmad Addo
Bioengineering 2026, 13(6), 605; https://doi.org/10.3390/bioengineering13060605 - 23 May 2026
Cited by 3 | Viewed by 422
Abstract
Consolidated bioprocessing (CBP), in which enzyme production, substrate hydrolysis, and fermentation occur in a single bioreactor, offers a promising pathway for lignocellulosic ethanol production. However, CBP operation involves competing objectives, including ethanol titer, volumetric productivity, substrate conversion, soluble sugar accumulation, batch duration, control [...] Read more.
Consolidated bioprocessing (CBP), in which enzyme production, substrate hydrolysis, and fermentation occur in a single bioreactor, offers a promising pathway for lignocellulosic ethanol production. However, CBP operation involves competing objectives, including ethanol titer, volumetric productivity, substrate conversion, soluble sugar accumulation, batch duration, control effort, and the operating severity associated with temperature and pH profiles. This study introduces a feasibility-aware multi-objective dynamic optimization framework for identifying Pareto-optimal operating policies for batch CBP. A reduced-order mechanistic model is developed to represent biomass growth, enzyme activity, insoluble substrate hydrolysis, soluble sugar formation and consumption, ethanol production, and inhibition under time-varying temperature and pH conditions. The optimization simultaneously maximizes ethanol titer, productivity, and substrate conversion while minimizing sugar accumulation, operating severity, control movement, and batch time. In the main simulation run, 120,000 dynamic policies were retained for analysis, resulting in 5017 feasible policies and 328 feasible Pareto-optimal policies under a minimum conversion threshold of 0.42. Within the feasible Pareto archive, the highest ethanol titer reached 1.265gL1, the highest productivity reached 0.017gL1h1, and the maximum conversion reached 0.440. Compared with the best criterion-specific static constant-operation baselines, the dynamic Pareto policies improved ethanol titer, productivity, and conversion by 10.6%, 8.3%, and 14.3%, respectively. A feasibility analysis showed that a conversion threshold of 0.42 was stringent but attainable, whereas thresholds of 0.44 and 0.55 were not attainable under the present model and operating bounds. Independent-seed repetitions confirmed a consistent high-performing region across stochastic searches. The resulting Pareto fronts and operating policy maps provide a model-based decision-support basis for selecting dynamic temperature and pH profiles for CBP operation. Because this study is in silico, future experimental validation is required before direct pilot- or industrial-scale application. Full article
(This article belongs to the Special Issue Strategies for Microbial Bioprocess Optimization)
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29 pages, 5506 KB  
Article
Ensuring Good Transferability from Pilot- to Large-Scale Optimized Biotech Bubble Column Designs
by Carolin Link, Jason Bromley, Michael Martin and Ralf Takors
Bioengineering 2026, 13(5), 579; https://doi.org/10.3390/bioengineering13050579 - 19 May 2026
Viewed by 570
Abstract
Scaling biotechnology processes such as gas fermentation remains resource- and time-intensive, both experimentally and in modeling. To improve the efficiency of reactor geometry optimization, we evaluated the transferability of findings from pilot-scale (950 L) simulations to industrial-scale simulations (950 m3). At [...] Read more.
Scaling biotechnology processes such as gas fermentation remains resource- and time-intensive, both experimentally and in modeling. To improve the efficiency of reactor geometry optimization, we evaluated the transferability of findings from pilot-scale (950 L) simulations to industrial-scale simulations (950 m3). At constant geometric ratios and aeration (vvm) across scales, highly similar flow patterns were observed, especially in airlift reactors. Reactor design enhancements at the pilot scale were transferable to the industrial scale, delivering improvements of up to 17% for kLa. Surprisingly, the commercial simulation resulted in an order-of-magnitude-higher gas holdup and kLa than the pilot, owing to a longer bubble residence time in the taller vessel. Thus, transferability can be further enhanced by enforcing constant superficial gas velocity between scales. This leads to more similar CO transfer rates and regime distributions inside the tank but will challenge reaching sufficient mass transfer for industrial applications. Full article
(This article belongs to the Special Issue Strategies for Microbial Bioprocess Optimization)
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