Mini Review - Pharmaceutical Bioprocessing (2023) Volume 11, Issue 3

Review on Fed-Batch Biomolecule Production by Bacillus Subtilis

Ozmadar Sahin*

Industrial Biotechnology and Metabolic Engineering Laboratory, Turkey

*Corresponding Author:
Ozmadar Sahin
Industrial Biotechnology and Metabolic Engineering Laboratory, Turkey

Received: 02-May-2023, Manuscript No. FMBP-23-99752; Editor assigned: 04-May-2023, PreQC No. FMBP-23-99752 (PQ); Reviewed: 18-May-2023, QC No FMBP-23-99752; Revised: 23-May-2023, Manuscript No. FMBP-23-99752 (R); Published: 30-May-2023, DOI: 10.37532/2048- 9145.2023.11(3).53-55


A modified batch culture approach or a step between batch and continuous fermentation procedures is fed-batch culture. Similar to batch culture, fed-batch culture’s products are collected in batches, or after the batch time. However, similar to the continuous fermentation process, the substrate is gradually introduced throughout the cultivation. However, like with batch fermentation, the amount of substrate needed to produce the desired products is unchanged. However, the fed-batch culture adds substrates intermittently at predetermined intervals rather than all at once. One of the most common commercial fermentation methods involves adding nutrients to the bioreactor on a regular or predetermined schedule in order to attain high cell biomass densities. As a result, fed-batch fermentation is a semi-continuous process in which products are kept in the bioreactor until the run and substrate is continuously added in tiny amounts. Overall, fedbatch culture has extended cell culture time while producing high-yield and high-quality proteins. In fed-batch culture, the feeding media is provided continuously or sporadically. The fed-batch culture has advanced significantly in recent years. Process development still depends on optimising feed components. Feed-batch culture should take into account culture parameters, nutrient consumption, and build-up of metabolic by products, etc. at the same time. We continue to consider key parameters, such as cell proliferation, the yield, and the quality of RTPs, as we further explore RTP generation in CHO cells. However, fedbatch culture has flaws in the process development area; selecting the best parameters, such as temperature, pH, dissolved oxygen, basal and feeding medium, and additives, can be difficult. Exploring a number of fantastic process parameters is restricted by a few variables [1-4].


Fermentation • Bioreactor • Concentration • Radiation


In its broadest definition, fed-batch culture is a method of operating in biotechnological processes where one or more nutrients (substrates) are fed (provided) to the bioreactor during cultivation and where the product(s) remain in the bioreactor until the conclusion of the run. An alternative way to describe the technique is as a culture where “a feed medium is added to prevent nutrient depletion and a base medium supports initial cell culture.” Additionally, it is a form of semi-batch culture. In rare instances, the bioreactor receives a complete supply of nutrients. The benefit of a fed-batch culture is the ability to control the concentration of fed-substrate in the culture medium at any arbitrary (and frequently low) desired level.

All of the substrates are added at the start of the fermentation, starting the process off like batch culture. Typically, the culture broth is only entirely or partially harvested at the conclusion of the operational period (the remaining portion acting as the inoculum for the following repeating run). A substrate is gradually supplied to the fed-batch culture as the fermentation develops. Small amounts of these substrates are applied throughout the production stage. There may be one or more feed streams present during operation, but there is no effluent. Since it is not possible to directly and continuously measure the substrate concentration, several indirect factors linked to substrate metabolism are measured in order to control the feeding process because of this, the culture volume [5-8].


By gradually introducing nutrient solution and composition into fermentation system that already includes a high-density bacterial culture, fed-batch operation is utilised to adjust the metabolic rates. Fed-batch fermentation is specifically used to get rid of stuff and dangerous inhibitors that are present in regular batch fermentation systems when the substrate concentration is high. In order to simultaneously reduce hazardous chemicals and increase butanol synthesis, upscale fed-batch fermentation was researched. To maximise the density of active bacteria and to give microorganism’s time to adjust to the fermentation medium, the fermenter was initially run in batch mode. After that, the substrate was introduced so that the enhanced bacteria could consume it adequately. As a result, the fermentation system no longer displayed substrate and/or product inhibition. A settling procedure is then used to eliminate supernatant included in main products once the fed-batch fermenter’s active volume is full. Then fed-batch action is repeated for a new cycle to begin. To balance the proportion of active cells in the fed-batch system, settled bacteria are partially eliminated from aged cells. In essence, a living cell from a microbial, plant, or animal source is a growing and dividing biochemical reactor where a lot of biochemical reactions are catalysed by enzymes. Live microbial cells are used in tissue cultures, whereas live plant or animal cells are used in microbial cultures. Similar to chemical and biochemical operations, these cultures can be operated in one of three standard operational modes: batch, continuous, or semi-batch (semicontinuous). Due to the rising need for unique chemicals and products as well as the benefits semi-batch reactors offer, their use has increased dramatically over the past three decades in the fermentation, biotechnology, chemical, and waste-treatment industries. In order to handle often low-volume, high-value items like fermentation products, batch and semi-batch methods are used [9,10].


Batch fermentation has been altered to become fed-batch fermentation. It was essentially created to get around batch fermentation’s restrictions. Fed-batch fermentation initially functions in a manner similar to batch fermentation up until the culture reaches the end of the log phase. When the culture reaches the log phase, regulated nutrient feeding is applied. High product yield is attained because this feeding prolongs the log phase. The feeding is done in a controlled manner because excessive uncontrolled feeding might saturate the microbial colony in fed-batch fermentation. The undiluted culture is fed as a limiting substrate in a fixed volume fed-batch culture. Radiation can impede development in a photosynthetic culture without influencing the culture’s volume. A fed-batch with variable volume is one in which the substrate feed causes the volume to change as the fermentation period progresses. A single fed-batch process, cyclic fedbatch culture, and repeating fed-batch processes are further categories for variable systems.


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