7.2 Industrial fermentation processes

Industrial fermentation processes are the backbone of microbial biotechnology. These methods harness microorganisms to produce valuable compounds like enzymes, antibiotics, and biofuels on a large scale.

From solid-state to submerged fermentation, various techniques are used. Bioreactors, process optimization, and scale-up are key to successful industrial fermentation. Upstream and downstream processing ensure efficient production and product recovery.

Fermentation Processes

Types of Fermentation

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• Solid-state fermentation involves the growth of microorganisms on solid substrates in the absence or near absence of free water
  • Commonly used for the production of enzymes, organic acids, and secondary metabolites
  • Offers advantages such as higher product concentration, lower energy requirements, and reduced wastewater generation compared to submerged fermentation
• Submerged fermentation is carried out in liquid media, where the microorganisms are suspended in the fermentation broth
  • Widely employed for the production of antibiotics, amino acids, and other valuable compounds
  • Provides better control over process parameters such as temperature, pH, and oxygen transfer, enabling more efficient fermentation

Process Optimization and Scale-up

• Scale-up involves the transfer of a fermentation process from laboratory scale to industrial scale while maintaining product quality and yield
  • Requires careful consideration of factors such as mixing, oxygen transfer, and heat removal to ensure consistent performance at larger scales
  • Pilot-scale studies are often conducted to identify and address potential challenges before full-scale implementation
• Process optimization aims to improve the efficiency and productivity of fermentation processes
  • Involves the manipulation of various parameters such as temperature, pH, agitation speed, and nutrient composition to enhance microbial growth and product formation
  • Design of experiments (DOE) and statistical tools like response surface methodology (RSM) are employed to identify optimal conditions for fermentation

Bioreactor Types

Stirred Tank Reactor (STR)

• Stirred tank reactors are the most common type of bioreactor used in industrial fermentation processes
  • Consist of a cylindrical vessel equipped with an agitator (impeller) for mixing and aeration
  • Provide good mixing and oxygen transfer, making them suitable for aerobic fermentations
  • Can be operated in batch, fed-batch, or continuous mode depending on the process requirements
• Bioreactor design considerations for STRs include impeller type, baffles, and sparger design to optimize mixing and gas dispersion
  • Rushton turbines and pitched blade impellers are commonly used for their ability to generate high shear and improve oxygen transfer
  • Baffles are installed to prevent vortex formation and improve mixing efficiency

Airlift Reactor (ALR)

• Airlift reactors utilize the principle of gas-liquid mass transfer to achieve mixing and aeration without the need for mechanical agitation
  • Consist of a riser section where gas is sparged, causing liquid circulation, and a downcomer section for liquid return
  • Suitable for shear-sensitive microorganisms and cell cultures due to the gentle mixing provided by the gas-induced circulation
• ALRs offer advantages such as lower shear stress, reduced energy consumption, and simplified reactor design compared to STRs
  • Particularly useful for the cultivation of plant and animal cells, as well as the production of biopolymers and other shear-sensitive products
  • Can be further classified into internal-loop and external-loop configurations based on the arrangement of the riser and downcomer sections

Production Stages

Upstream Processing

• Upstream processing refers to the steps involved in the preparation of the fermentation medium and inoculum before the main fermentation process
  • Includes media preparation, sterilization, and inoculum development to ensure optimal conditions for microbial growth
  • Media composition is tailored to the specific requirements of the microorganism and the desired product
  • Sterilization techniques such as heat sterilization (autoclaving) or filtration are employed to prevent contamination
• Inoculum development involves the preparation of a viable and active microbial culture to initiate the fermentation process
  • Typically starts with a small-scale culture (seed culture) that is progressively scaled up to the desired volume for inoculation
  • Ensures that the microorganisms are in the appropriate growth phase and at sufficient cell density to achieve efficient fermentation

Downstream Processing and Product Recovery

• Downstream processing encompasses the steps following fermentation, aimed at separating and purifying the desired product from the fermentation broth
  • Involves various unit operations such as centrifugation, filtration, extraction, chromatography, and crystallization, depending on the nature of the product
  • Centrifugation is commonly used for cell separation and clarification of the fermentation broth
  • Filtration techniques like microfiltration and ultrafiltration are employed for further clarification and concentration of the product
• Product recovery refers to the final stages of downstream processing, where the purified product is isolated and formulated into its final form
  • May involve processes such as drying, crystallization, or lyophilization to obtain a stable and easily handleable product
  • Quality control tests are performed to ensure that the product meets the required specifications for purity, potency, and safety before release
• The choice of downstream processing methods depends on the physicochemical properties of the product, such as size, charge, and solubility
  • Optimization of downstream processing is crucial for maximizing product recovery and minimizing costs
  • Integration of upstream and downstream processes is essential for the overall efficiency and economics of the fermentation process