Industrial Fermentation: Definition, Problem and Application

What is industrial fermentation?

Industrial fermentation refers to a biotechnological process of significant scale that employs microorganisms, including bacteria, yeasts, and fungus, to generate useful compounds by controlled fermentation. This technique is crucial in several sectors, including as medicines, food and beverages, biofuels, and chemicals. Microbiological optimization is the application of advanced equipment and techniques to maximize the development of microorganisms and ensure high product production. Processes in industrial fermentations encompass both upstream (USP) and downstream processing (DSP) phases. The USP framework encompasses three primary domains: (1) the organism responsible for production, (2) the culture medium, and (3) the process of fermentation. DSP encompasses all phases subsequent to the fermentation process. The complexities of DSP are conditioned by the necessary level of purity of the end result, which is subsequently influenced by its intended use and market worth. The primary goal of DSP is to efficiently retrieve the final product according to its specified requirements, while also seeking to get the highest possible product output at feasible expenses.

A summary of major steps in industrial fermentation. (Mukherjee S, 2019)

A picture of industrial scale bioreactor fermenters. (Mazzeo L, et al., 2020)

Fermentation technology at BOC Sciences

• Aerobic Fermentation
• Anaerobic Fermentation
• Continuous Fermentation & Fed-Batch Fermentation
• Solid State Fermentation (SSF)
• Submerged Fermentation (SmF)
• Fermentation CDMO
• Downstream Process Optimization
• Upstream Process Optimization

Applications for industrial fermentation

Pharmaceuticals: Industrial fermentation is employed for the synthesis of antibiotics like penicillin, streptomycin, and tetracycline. The synthesis of these medications by microorganisms such as Penicillium chrysogenum and Streptomyces griseus is crucial for the treatment of bacterial infectious diseases. Insulin, human growth hormones, and monoclonal antibodies are recombinant proteins that are synthesised by genetically modified microbes. These proteins have a crucial role in the treatment of illnesses such as diabetes, cancer, and autoimmune disorders. The production of vaccines for illnesses such as influenza, hepatitis, and COVID-19 involves the process of fermentation. Cultural cultivation of microorganisms or viral vectors is employed to generate antigens or viral proteins, which then serve to elicit immunological responses.

For foods: In the food and beverage sector, industrial fermentation is employed for the production of alcoholic beverages such as beer and wine, fermented foods like cheese and yogurt, and food additives including enzymes and organic acids. Enzymes such as amylases, proteases, and lactases are synthesised during fermentation. They are employed in food processing to augment flavors, textures, and prolong the shelf life of food products. Citric acid, lactic acid, and glutamic acid are synthesised by the process of fermentation and employed in food products as agents to augment taste, preserve, and control pH levels.

For energy: Bioethanol and other biofuels are created from biomass through industrial fermentation. This method helps establish sustainable energy sources and minimize dependency on fossil fuels.

Applications of fermentation technology at BOC Sciences

• Fermentation in Pharmaceuticals
• Fermentation for Special Small Molecules
• Fermentation in Human Nutrition
• Fermentation in Animal Health
• Fermentation in Agriculture
• Fermentation for Pigments
• Fermentation for Feed Additives

Industrial fermentation problems

Contamination: Excessive proliferation of undesired microorganisms, such as bacteria or fungus, can pollute the fermentation process, resulting in diminished production and quality. Contamination may originate from equipment, raw materials, or sources in the environment.

Process control issues: The maintenance of a constant temperature is essential for achieving the best possible microbial activity. Deviation from the norm might impact fermentation rates and product yields. Variations in pH can affect microbial metabolism and enzyme function, resulting in varying quality of products. Lack of sufficient oxygen supply in aerobic fermentation might restrict the development of microorganisms and the production of products.

Cost management: The initial concentration of the product is the primary determinant of costs in the whole manufacturing process. Given the significant variations in size and characteristics of the products, it is necessary to use distinct separation methods for their isolation and purification. The impact of each isolation stage, as well as the total number of purification stages, leads to substantial operational expenses, even if the average yield of each stage ranges from 80% to 90%. Thus, in order to achieve maximum economic viability, the number of processes needed to meet the specified product standards should be reduced.

Product inhibition: The buildup of metabolic by-products, such as ethanol or organic acids, can impede the development of microorganisms and hence decrease the efficiency of fermentation. Elevated levels of substrates or inhibitors can hinder microbial activity.

Genetic heterogeneity: Biological populations, regardless of their engineering status, experience ongoing evolution through many processes at rates ranging from 10–2 to 10–10 per base pair every generation. The primary consequence of base substitutions in fermentations aimed at generating metabolites and enzymes is the reduction of enzyme activity. Loss-of-function mutation rates of around 10–8 per base pair per generation are seen in CHO cell lines employed for the synthesis of therapeutic proteins in mammals. Such rates can be adequate to undermine the quality of the output, even when small-scale agriculture is involved.

Evolution of heterogeneity during industrial fermentation. (Rugbjerg P., et al., 2019)

How to optimize industrial fermentation?

Process optimization: Entails maintaining accurate temperature control within the bioreactor to enable optimal microbial growth and metabolic activity. Use sophisticated temperature control systems and sensors to monitor and alter temperatures in real time. Monitor and regulate the pH of the fermentation medium to keep it in the ideal range for microorganisms. Use pH sensors to automatically supply acids and bases as required. Ensure an appropriate oxygen supply for aerobic fermentation processes. Employ aeration equipment, such as spargers or oxygen-enriched air, and use sensors to monitor dissolved oxygen levels. Create and maintain a well-balanced fermentation medium that contains all of the required elements, such as carbon, nitrogen, vitamins and minerals. Nutrient concentrations should be analyzed and adjusted on a regular basis to fulfill the needs of microorganisms. Use suitable feeding techniques, such as batch, fed-batch, or continuous feeding, to maintain microbial activity and maximize product production. Use agitation devices to stir the fermentation media uniformly, minimizing microbial clumping and guaranteeing even distribution of nutrients and oxygen. Optimize the impeller design, speed, and bioreactor shape to improve mixing efficiency and minimize energy usage.

Scale-Up and process development: Prior to scaling up to industrial levels, do pilot-scale studies to evaluate and improve fermentation conditions. This assists in identifying possible difficulties and refining process parameters. Scale-up models and simulations may be used to forecast and steer changes to the fermentation process at bigger sizes. Implement automation and control systems to monitor and regulate fermentation parameters, therefore eliminating manual intervention and increasing consistency.

Microbial strain optimization: Utilize genetic modification methodologies to augment the functionality of microbial strains, such as enhancing their resistance to by-products or augmenting their synthesis of targeted metabolites. Thoroughly evaluate and choose strains that exhibit excellent characteristics for fermentation, including high productivity, durability, and resilience to environmental pressures. Consistently monitor and maintain the stability of microbial strains to guarantee sustained long-term performance. Target and rectify any genetic drift or mutations that might impact the results of the procedure.

Scheme of theoretical steps and stages of fermentation process optimization and scale up. (Schmidt F R., 2005)

Relationship between industrial fermentation, the economy and the environment

Industrial fermentation exerts a significant influence on both the domestic economy and the natural environment. Although it stimulates economic expansion, fosters innovation, and generates employment opportunities, it also poses environmental issues that need meticulous scrutiny. In order to maximize the advantages of industrial fermentation while reducing its environmental effect, it is necessary to implement sustainable practices, optimize processes, and comply with legal frameworks. Maintaining this equilibrium is crucial for attaining enduring economic and environmental sustainability.

References

1. Mukherjee S. Isolation and purification of industrial enzymes: advances in enzyme technology[M]//Advances in Enzyme Technology. Elsevier, 2019: 41-70.
2. Mazzeo L., et al., Fermentation and biochemical engineering: principles and applications[M]//Studies in surface science and catalysis. Elsevier, 2020, 179: 261-285.
3. Rugbjerg P., et al., Overcoming genetic heterogeneity in industrial fermentations, Nature biotechnology, 2019, 37(8): 869-876.
4. Schmidt F R. Optimization and scale up of industrial fermentation processes, Applied microbiology and biotechnology, 2005, 68: 425-435.