Fermentation Processes: Modeling, Optimization and Control

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 27755

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Guest Editor
Center for Research and Advanced Studies of the National Polytechnic Institute, Cinvestav, Mexico City, Mexico
Interests: chemical reaction engineering; control theory; kinetics; reaction kinetics; process engineering; kinetic modeling; modeling and simulation; advanced control theory; system modeling; systems dynamics
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Special Issue Information

Dear Colleagues,

Fermentation processes play an important role in the transformation industry, such as food, pharmaceutical, biofuels, industrial metabolites, and so on. As a result, the demand is increasing for high-quality products with low-energy consumption and operational safety, which can operate within the context of the very complex nature of biological systems. This, however, has made process operations difficult, leading to the development of intensive engineering strategies to achieve these performance objectives. Therefore, modeling and simulation tasks for optimization and control purposes in fermentation equipment are incredibly important.

The main goal of this Special Issue is to include the latest developments and advancements in process fermentation technology and bioprocessing to achieve progress in key industrial sectors. Special attention will be given to research topics such as high predictive modeling techniques, detailed process simulations to characterize realizable operating conditions, applications of multiobjective optimization techniques with the newest mathematical techniques, the design of online estimation procedures for process monitoring purposes and new controller designs, and improvements to closed-loop operation performance.

Overall, the aim of this issue is to support the development of sustainability assessment tools to measure the socioeconomic and environmental performance of innovative technical advances for fermentation processes.

Dr. Ricardo Aguilar-López
Guest Editor

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

  • fermentation technology
  • process modeling
  • simulation analysis
  • process optimization
  • control process
  • sustainability issues

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Published Papers (12 papers)

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Research

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11 pages, 1229 KiB  
Article
Enhanced Succinic Acid Production and Electronic Utilization Efficiency by Actinobacillus succinogenes 130Z in an ORP-Controlled Microbial Electrolysis Cell System
by Jieyi Peng, Shuo Zhao, Ying Li, Zhen Wang and Li Chen
Fermentation 2024, 10(2), 109; https://doi.org/10.3390/fermentation10020109 - 17 Feb 2024
Viewed by 1213
Abstract
Microbial electrochemical systems have shown great value as a means of enhancing the efficiency of fermentation reactions, but at present, there is no reliable means to balance the extracellular electron supply and corresponding intracellular demands in these systems. The current work describes the [...] Read more.
Microbial electrochemical systems have shown great value as a means of enhancing the efficiency of fermentation reactions, but at present, there is no reliable means to balance the extracellular electron supply and corresponding intracellular demands in these systems. The current work describes the unique use of an oxidation–reduction-potential (ORP)-level-controlled microbial electrolysis cell (MEC) system to successfully balance the extracellular electron supply and succinic acid fermentation via A. succinogenes (130Z). The ORP-controlled MEC system with neutral red (NR) yielded a significant increase in succinic acid production (17.21%). The utilization of NR in this MEC system improved the ORP regulatory sensitivity. The optimal approach to the ORP level control was the use of a −400 mV high-voltage electric pulse-based strategy, which increased the yield of succinic acid by 13.08% compared to the control group, and reduced the energy consumption to 52.29% compared to the potentiostatic method. When compared to the −1 V constant potential MEC system, the high-voltage electric pulse-based ORP strategy for the MEC system control provided sufficient electrons to this system while using less electricity (11.96%) and producing 12.48% (74.43 g/L) more succinic acid during fed-batch fermentation. The electronic utilization efficiency of the ORP-controlled MEC system was 192.02%, which was 15.19 times that of the potentiostatic system. The electronic utilization efficiency is significantly increased in the ORP-controlled MEC system. Succinic acid production is ensured by a high-voltage electric pulse-based method, while the influence on cell growth and power consumption are minimized. Fed-batch fermentation with the high-voltage electric pulse-based ORP strategy for MEC system control is noted to be ideal to achieve a further increase in succinic acid concentration and electronic utilization efficiency. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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15 pages, 3057 KiB  
Article
Comparative Study of the Extracellular Holocellulolytic Activity of Fusarium solani and Aspergillus sp. in Corn Stover
by Mariana Alvarez-Navarrete, Katia L. Alonso-Hurtado, Alberto Flores-García, Josué Altamirano-Hernández, Mauro M. Martínez-Pacheco and Crisanto Velázquez-Becerra
Fermentation 2024, 10(2), 84; https://doi.org/10.3390/fermentation10020084 - 30 Jan 2024
Viewed by 1269
Abstract
Fungal holocellulases are interesting for their possible applications in the bioconversion of corn crop residues into molecules with technological significance. Holocellulase (xylanases and cellulases) production from Fusarium solani and Aspergillus sp. with corn stover as a carbon source was compared using a Box–Wilson [...] Read more.
Fungal holocellulases are interesting for their possible applications in the bioconversion of corn crop residues into molecules with technological significance. Holocellulase (xylanases and cellulases) production from Fusarium solani and Aspergillus sp. with corn stover as a carbon source was compared using a Box–Wilson design. The fungal holocellulase production was different in both fungi. For F. solani, the maximum endoxylanase and β-xylosidase activities were 14.15 U/mg and 0.75 U/mg at 84 h of fermentation on 350 g/L corn stover, while Aspergillus sp. was 5.90 U/mg and 0.03 U/mg, respectively, at 156 h and 1000 g/L corn stover. The production of holocellulases in both fungi was reduced with increasing carbon sources. The nitrogen source induced the holocellulases in Aspergillus sp., but not in F. solani. Interestingly, when verifying the optimal culture conditions, the production of endoxylanases by F. solani was higher when compared to the predicted value. With regard to the endoxylanase and β-xylosidase activities of Aspergillus sp., these were close to the predicted values. Based on the optimization model, F. solani and Aspergillus sp. produce an interesting holocellulolytic activity in a growth medium with corn stover as the only carbon source. The fermentation time and the amount of corn stover required to obtain maximum holocellulase production are possible advantages for Fusarium solani and Aspergillus sp., respectively. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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11 pages, 2342 KiB  
Communication
Bioprocess Intensification of a Continuous-Flow Enzymatic Bioreactor via Productivity Dynamic Optimization under Modeling Uncertainty
by Ricardo Femat, Ricardo Aguilar-López and Juan L. Mata-Machuca
Fermentation 2024, 10(1), 11; https://doi.org/10.3390/fermentation10010011 - 21 Dec 2023
Viewed by 1193
Abstract
In this contribution, a class of observer-based optimal feedback control is designed. The proposed feedback control is based on the Euler–Lagrange theoretical framework, and it is motivated by the productivity intensification from the chemical reactors, which is optimally increased. A Lagrangian is computed [...] Read more.
In this contribution, a class of observer-based optimal feedback control is designed. The proposed feedback control is based on the Euler–Lagrange theoretical framework, and it is motivated by the productivity intensification from the chemical reactors, which is optimally increased. A Lagrangian is computed by employing the corresponding mass balance equation of a specifically selected biochemical compound. The resulting optimal controller is coupled with a novel uncertainty estimator with bounded feedback to derive an accurate estimation of the unknown terms and functions, mostly related to the reaction rate. Via Lyapunov analysis, it was shown that the proposed observer is asymptotically stable. The estimation of the unknown terms and functions is used by the proposed controller. The proposed methodology is applied to a generic model of an enzymatic biochemical continuous reactor with complex oscillatory dynamic behavior described by mass balance equations, so, in general, the proposed controller may be applied to any continuous stirred tank bioreactor; that is, the controller is independent of the specific kinetic functions. Numerical simulations show a satisfactory performance of the proposed control strategy. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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17 pages, 2399 KiB  
Article
Optimization of a Bacterial Cultivation Medium via a Design-of-Experiment Approach in a Sartorius Ambr® 15 Fermentation Microbioreactor System
by Antonio Baccante, Pasquale Petruccelli, Giovanni Saudino, Elena Ragnoni, Erik Johansson, Vito Di Cioccio and Kleanthis Mazarakis
Fermentation 2023, 9(12), 1002; https://doi.org/10.3390/fermentation9121002 - 27 Nov 2023
Viewed by 2177
Abstract
In the evolving landscape of sustainable biopharmaceutical process development, the utilization of bacteria in the production of various compounds via fermentation has attracted extensive attention from scientists. A successful fermentation process and the release of its associated products hinge on the synergy between [...] Read more.
In the evolving landscape of sustainable biopharmaceutical process development, the utilization of bacteria in the production of various compounds via fermentation has attracted extensive attention from scientists. A successful fermentation process and the release of its associated products hinge on the synergy between an efficient bacterial strain and the formulation of a suitable growth medium. Balancing all nutrient levels of a growth medium to maximize microbial growth and the product quality is quite an intricate task. In this context, significant advancements have been achieved via the strategic implementation of design-of-experiment (DOE) methodologies and the utilization of parallel microbioreactor systems. This work presents a case study of the fermentation growth medium optimization of a Gram-negative bacterium of the Neisseriaceae family that releases outer membrane vesicles (OMVs), which represent a potential vaccine platform. To achieve this, the ability of Sartorius MODDE®13 DOE software to explore multiple variables and their interactions was combined with the functionality of a Sartorius Ambr® 15F parallel microbioreactor system. The findings reported in this study have led to the design of a well-suited fermentation medium for a Gram-negative bacterium and an improvement in the quality of the OMVs produced from it. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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17 pages, 10207 KiB  
Article
Monitoring β-Fructofuranosidase Activity through Kluyveromyces marxianus in Bioreactor Using a Lab-Made Sequential Analysis System
by Edwin J. Barbosa-Hernández, Jorge E. Pliego-Sandoval, Anne Gschaedler-Mathis, Javier Arrizon-Gaviño, Alejandro Arana-Sánchez, Ricardo Femat and Enrique J. Herrera-López
Fermentation 2023, 9(11), 963; https://doi.org/10.3390/fermentation9110963 - 10 Nov 2023
Viewed by 1859
Abstract
The yeast Kluyveromyces marxianus has shown the potential to produce β-fructofuranosidases, which are enzymes capable of hydrolyzing β-fructofuranosides links of fructans to obtain fructooligosaccharides. The thriving market for fructose syrup and the quality standards imposed by food and pharmaceutical industries have [...] Read more.
The yeast Kluyveromyces marxianus has shown the potential to produce β-fructofuranosidases, which are enzymes capable of hydrolyzing β-fructofuranosides links of fructans to obtain fructooligosaccharides. The thriving market for fructose syrup and the quality standards imposed by food and pharmaceutical industries have generated an increased search for improved, monitored, and controlled production processes. Monitoring β-fructofuranosidase activity in a bioprocess requires the use of adequate sensors and the processing of information using efficient software algorithms; nevertheless, currently, such a sensor does not exist for this purpose. In this contribution, a sequential injection analysis system (SIA) developed in our laboratory was adapted to monitor at-line β-fructofuranosidase activity produced by the yeast K. marxianus. Samples were taken out automatically from the bioreactor and analyzed using 3,5-dinitrosalicylic (DNS). An algorithm was designed to operate the overall components of the lab-made SIA system. The enzymatic activity error obtained with the automatic SIA compared to the off-line laboratory determinations varied from 0.07% at high enzyme concentrations to 20.39% at low β-fructofuranosidase activity. Further development is required to improve the performance of the lab-made SIA system; nevertheless, such a device must be considered as a potential method for monitoring β-fructofuranosidase activity in real time. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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13 pages, 8875 KiB  
Article
Design Optimization of a Tray Bioreactor for Solid-State Fermentation: Study of Process Parameters through Protein Modification of By-Products
by Pau Sentís-Moré, María-Paz Romero-Fabregat, Cristina Rodríguez-Marca, Antonio-Jesús Guerra-Sánchez and Nàdia Ortega-Olivé
Fermentation 2023, 9(10), 921; https://doi.org/10.3390/fermentation9100921 - 23 Oct 2023
Cited by 1 | Viewed by 2042
Abstract
This study investigated the design of a tray bioreactor for solid-state fermentation, applying Rhizopus oryzae to oilseed meals as the substrate. Two process variables were continuously monitored in the bioreactor to ensure precise control of the environmental conditions: temperature and relative humidity (RH). [...] Read more.
This study investigated the design of a tray bioreactor for solid-state fermentation, applying Rhizopus oryzae to oilseed meals as the substrate. Two process variables were continuously monitored in the bioreactor to ensure precise control of the environmental conditions: temperature and relative humidity (RH). The comprehensive analysis covered the effects of different fermentation conditions on the protein content, technological properties, and molecular distribution of the samples. The study revealed that the configuration factors suffered a stratification within the three trays of the bioreactor. Notably, the upper tray registered the largest dispersion, with a range of 1.5 °C. When analyzing the differences between sensors within each tray, the largest difference was found in the lower tray (10.9%). Furthermore, higher EAI (Emulsifying Activity Index) values were observed in the upper tray (T3) for rapeseed. As for ESI (Emulsion Stability Index) values, no differences were observed between the trays or fermentation periods. Using the changes induced by Rhizopus oryzae fungal enzymes, the study quantitatively examined the changes in the by-product valorization. While the bioreactor factors did not affect the protein quantity itself, they had significant impacts on specific changes within the molecular weight protein fraction. The findings of this study offer significant insights into the complex dynamics of solid-state fermentation processes. The outcomes of this study not only advance understanding of solid-state fermentation but also offer practical guidance for the design and operation of fermenters in industrial applications. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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13 pages, 334 KiB  
Article
Acquisition, Characterization, and Optimization of Distilled Bioethanol Generated from Fermented Carrot (Daucus carota) Residues
by Abraham Palacios-Velásquez, Violeta Quispe-Coquil, Enzo Martín Casimiro-Soriano, Karla Milagros Tapia-Zarate and Alex Rubén Huamán-De la Cruz
Fermentation 2023, 9(10), 867; https://doi.org/10.3390/fermentation9100867 - 25 Sep 2023
Viewed by 1337
Abstract
Bioethanol is a liquid biofuel produced from the digestion of biomass and usable waste of organic origin. The objective of this research was to obtain bioethanol from carrot (Daucus carota) residues of the Peruvian Chantenay variety, with a high content of [...] Read more.
Bioethanol is a liquid biofuel produced from the digestion of biomass and usable waste of organic origin. The objective of this research was to obtain bioethanol from carrot (Daucus carota) residues of the Peruvian Chantenay variety, with a high content of lignocellulosic substances. The in-batch process method of enzymatic hydrolysis, with Aspergillus niger amyloglucosidase, and fermentation, with Saccharomyces cerevisiae yeast, was applied. The ferment was steam distilled and chemically characterized. The process was evaluated by controlling pH and enzyme/yeast mass ratio through the response surface optimization. The optimum conditions for the best values of TSS and % ethanol content for the distilled product were a time of 300 min, yeast/enzyme mass ratio of 24.0, and pH of 4.98. The results showed a significant decrease in sugars in the hydrolysis and fermentation stages, optimum alcohol content in the distilled product of 92.48% (v/v), lower organic compound content, and net calorific value of 23.82 MJ/kg, which is higher than those reported in the literature. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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16 pages, 3986 KiB  
Article
Design and Construction of a New Reactor for Flexible Biomethanation of Hydrogen
by Kevin Hoffstadt, Dheeraja Cheenakula, Marcell Nikolausz, Simone Krafft, Hauke Harms and Isabel Kuperjans
Fermentation 2023, 9(8), 774; https://doi.org/10.3390/fermentation9080774 - 19 Aug 2023
Cited by 3 | Viewed by 1341
Abstract
The increasing share of renewable electricity in the grid drives the need for sufficient storage capacity. Especially for seasonal storage, power-to-gas can be a promising approach. Biologically produced methane from hydrogen produced from surplus electricity can be used to substitute natural gas in [...] Read more.
The increasing share of renewable electricity in the grid drives the need for sufficient storage capacity. Especially for seasonal storage, power-to-gas can be a promising approach. Biologically produced methane from hydrogen produced from surplus electricity can be used to substitute natural gas in the existing infrastructure. Current reactor types are not or are poorly optimized for flexible methanation. Therefore, this work proposes a new reactor type with a plug flow reactor (PFR) design. Simulations in COMSOL Multiphysics ® showed promising properties for operation in laminar flow. An experiment was conducted to support the simulation results and to determine the gas fraction of the novel reactor, which was measured to be 29%. Based on these simulations and experimental results, the reactor was constructed as a 14 m long, 50 mm diameter tube with a meandering orientation. Data processing was established, and a step experiment was performed. In addition, a kLa of 1 h−1 was determined. The results revealed that the experimental outcomes of the type of flow and gas fractions are in line with the theoretical simulation. The new design shows promising properties for flexible methanation and will be tested. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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12 pages, 2902 KiB  
Article
Mathematical Modeling of Nitrification in Mixed Cultures: Insights into Nitrite-Oxidizing Bacteria Growth and Ammonia Starvation Effect
by Georgios Manthos, Leila Abbaszadeh, Dimitris Zagklis and Michael Kornaros
Fermentation 2023, 9(7), 681; https://doi.org/10.3390/fermentation9070681 - 20 Jul 2023
Viewed by 1481
Abstract
Nitrification, a crucial process in wastewater treatment, involves the conversion of ammonium nitrogen to nitrate nitrogen through the sequential activities of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB). In the present study, a comprehensive mathematical model was developed to describe the nitrification process [...] Read more.
Nitrification, a crucial process in wastewater treatment, involves the conversion of ammonium nitrogen to nitrate nitrogen through the sequential activities of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB). In the present study, a comprehensive mathematical model was developed to describe the nitrification process in mixed cultures involving isolated NOB and starved AOB. The growth equation for NOB was divided into anabolism and catabolism, elucidating the key substrates driving their metabolic activities. Considering the ammonia starvation effect, a single cell-based model was developed to capture the mass transfer phenomena across the AOB cell membrane. This addition allowed for a more accurate representation of the biological dynamics during starvation conditions. The model’s accuracy was tested using experimental data that was not used in the model calibration step. The prediction’s coefficient of determination (R2) was estimated at 0.9. By providing insights into the intricate mechanisms underlying nitrification, this model contributes to the advancement of sustainable wastewater treatment practices. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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13 pages, 1870 KiB  
Article
Production of Glyoxylate from Glucose in Engineered Escherichia coli
by Bui Hoang Dang Long, Masahiro Nishiyama, Rintaro Sato, Tomonari Tanaka, Hitomi Ohara and Yuji Aso
Fermentation 2023, 9(6), 534; https://doi.org/10.3390/fermentation9060534 - 31 May 2023
Cited by 2 | Viewed by 2391
Abstract
Glyoxylates are essential intermediates in several metabolic pathways and have a broad range of industrial applications. In this study, we propose a novel method for producing glyoxylate from glucose using engineered Escherichia coli BW25113. To direct the production of glyoxylate from glucose, malate [...] Read more.
Glyoxylates are essential intermediates in several metabolic pathways and have a broad range of industrial applications. In this study, we propose a novel method for producing glyoxylate from glucose using engineered Escherichia coli BW25113. To direct the production of glyoxylate from glucose, malate synthase A (aceB), malate synthase G (glcB), glyoxylate carboligase (gcl), and glyoxylate/hydroxypyruvate reductase A (ycdW) genes were disrupted, and the glyoxylate shunt was reinforced in the disruptants by the overexpression of citrate synthase (gltA) and isocitrate lyase (aceA). In flask cultivation using M9 medium supplemented with 1% glucose, the disruptant E. coli BW25113 ΔaceB ΔglcB Δgcl ΔycdW produced 0.93 ± 0.17 g/L of glyoxylate. Further overexpression of gltA and aceA in the disruptant resulted in an improvement in glyoxylate production to 1.15 ± 0.02 g/L. By expressing a heterologous gene, pyc, in the engineered E. coli, the accumulation of intracellular oxaloacetate remarkably improved, leading to glyoxylate production of up to 2.42 ± 0.00 g/L with specific productivity at 4.22 ± 0.09 g/g-cell. To date, this is the highest reported titer and specific productivity of glyoxylate in E. coli. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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19 pages, 2862 KiB  
Article
Improving the Functionality of Lentil–Casein Protein Complexes through Structural Interactions and Water Kefir-Assisted Fermentation
by Mohammad Alrosan, Thuan-Chew Tan, Azhar Mat Easa, Muhammad H. Alu’datt, Carole C. Tranchant, Ali Madi Almajwal, Sana Gammoh, Sofyan Maghaydah, Mohammed Ali Dheyab, Mahmood S. Jameel and Ali Al-Qaisi
Fermentation 2023, 9(2), 194; https://doi.org/10.3390/fermentation9020194 - 20 Feb 2023
Cited by 13 | Viewed by 3041
Abstract
Highly nutritious lentil proteins (LP) have recently attracted interest in the food industry. However, due to their low solubility, extensive application of LP is severely limited. This study describes a new and successful method for overcoming this challenge by improving the nutritional–functional properties [...] Read more.
Highly nutritious lentil proteins (LP) have recently attracted interest in the food industry. However, due to their low solubility, extensive application of LP is severely limited. This study describes a new and successful method for overcoming this challenge by improving the nutritional–functional properties of LP, particularly their solubility and protein quality. By combining protein complexation with water kefir-assisted fermentation, the water solubility of native LP (~58%) increases to over 86% upon the formation of lentil–casein protein complexes (LCPC). Meanwhile, the surface charge increases to over −40 mV, accompanied by alterations in secondary and tertiary structures, as shown by Fourier-transform infrared and UV-vis spectra, respectively. In addition, subjecting the novel LCPC to fermentation increases the protein digestibility from 76% to over 86%, due to the reduction in micronutrients that have some degree of restriction with respect to protein digestibility. This approach could be an effective and practical way of altering plant-based proteins. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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Review

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15 pages, 2404 KiB  
Review
Biosynthesis of Nicotinamide Mononucleotide: Current Metabolic Engineering Strategies, Challenges, and Prospects
by Shiqi Luo, Juntao Zhao, Yangyang Zheng, Tao Chen and Zhiwen Wang
Fermentation 2023, 9(7), 594; https://doi.org/10.3390/fermentation9070594 - 26 Jun 2023
Cited by 3 | Viewed by 6455
Abstract
Nicotinamide mononucleotide (NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+), which is widely applied in the pharmaceutical and biotech industries. The biosynthesis of NMN is currently attracting much attention because it has non-toxic reaction conditions and low amounts of [...] Read more.
Nicotinamide mononucleotide (NMN) is an essential precursor of nicotinamide adenine dinucleotide (NAD+), which is widely applied in the pharmaceutical and biotech industries. The biosynthesis of NMN is currently attracting much attention because it has non-toxic reaction conditions and low amounts of isomers, whereas chemical synthesis has low yields and is not environmentally friendly. This review systematically describes the two biosynthetic pathways of NMN in detail for the first time and introduces the latest studies on NMN production through different pathways using metabolic engineering strategies. NMN accumulation can be improved by optimizing the activity of key enzymes, enhancing the supply of precursors and co-factors, inhibiting the synthesis of byproducts, and promoting product export. Finally, we also discuss the current challenges of producing NMN and possible solutions for the future. Full article
(This article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control)
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