Modes of Fermenter Operation 1

Batch and Fed-batch fermentation

Pramono, H.
 You may read
Sue Macauley-Patrick and Beverley Finn, Practical
Fermentation Technology
 Introduction
The purpose of this presentation is to describe (briefly)
various modes of operation avaiable for fermentation
Large quantity of products, production, nature of
secondary metabolites production different modes
of fermentation
Based on modes:
Batch fermentation
Fed-batch fermentation
Batch continuous fermentation
Graphicaly

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 Batch culture
Batch fermentation is the simplest mode of operation,
and often used in laboratory to obtain substantial
quantities of cells or products for further analysis
Close system, in one batch containing:
Nutrient
Starter microbes
In end fermentation process the batch containing:
Nutrient (depleted)
Starter microbes
Product(s)
 Termination of fermentation process

The fermentation is terminated when one or more of

the following has been reached:
1. Microbial growth has stopped due to the
depletion of the nutrients or the build of toxic
compounds
2. After fixed predetermined period of time
3. The concentration of desired product has been
achieved
 Batch culture growth curve
When cells are grown in a batch culture, they will
typically proceed through a number of distinct
phase
Lag phase (may or may not be present) must be
minimize, how?
Log phase
Stationary
Initial of death

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Growth of associated product (primary
metabolites)

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 Growth associated product

Example of commercial growth associated products

Ethanol produced bay Saccharomyces cerevisiae
Amino acid (MSG) produced by Corynebacterium
glutamacium
Riboflavin produced by Ashbya gossipii
Citic acid produced by Aspergillus niger
Xanthan gum produced by Xanthonomonas campestris
Vitamin B12 produced by Pseudomonas denitrificans
 Secondary metabolites

Most antibiotics are produced as secondary

metabolites
Fermentation can then stopped just before the cells
enter the death phase
 Advantages of batch culture

1. Simplicity of use
2. Operability and reliability
3. Production of secondary metabolites that are not
growth-related
4. Fewer possibilities of contamination
5. Easy to assign a unique batch number to each run
 Disadvantages of batch culture

1. Culture ageing, differentiation bad production

2. Build up toxic metabolites can be restrict cell growth
and product formation
3. Initial substrates concentrations may have to be
limited due to problems with inhibition and
repression (like: carbon repression)
4. Batch to batch variability
5. Non productive periods to maintain the facilities
6. Degeneration of production
7. Heterogeneous and constantly changing culture
 Fed-batch culture

Fed-batch culture is essentially similar to batch

culture
Most of fed-batches begin live with a straighforward
batch phase
Different: do not operate as closed systems
The different feeding regiment, different growth/
process inside the batch
Various curve vs Batch culture
Variable feeding regime

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Continuous feeding regime

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Intermittent feeding regime
Incremental feeding regime
 Advantages and disadvantages of various feeding
strategies
Feeding strategy Advantages
Variable Minimizing by-product
formation
Substrate converted to
biomass, product or both
Continuous Allow bioprocess to run
without operator control
Intermittent Allows feed to be fully utilised
before further addition
Reducing catabolite
repression
Incremental Allows feed to increase with
biomass formation
Optimizing growth rate and
product formation
Disadvantages
Controlled by feedback
control
Requires accurate monitoring
and operator control
Must have historical process
trend data
Controlled by feedback
control
Requires accurate monitoring
and operator control
Controlled by feedback
control
Requires accurate monitoring
and operator control
 Advantages of Fed-batch Culture
1. Controlling the concentration of the limiting substrate
prevent repressive effects of high substrate
concentration
2. Avoids catabolite repression
3. High cell density (up to ten times compared to batch
culture)
4. Increased production of non-growth-related
secondary metabolites
5. Reduction of broth viscosity
Disdvantages of Fed-batch Culture
1. Detailed knowledge of the organisms growth and
product formation pattern is required
2. Deficiency of reliable online sensors for accurate
substrate determination in near real time
3. Without feedback control, fed is predetermined
and therefore does not allow for any fluctuation
within the bioprocess
4. The process operator must be fully trained and
highly skilled
 Batch and Fed-batch features
1. Small quantities of products can be obtain from
laboratory production
2. Products may not able to be stored for long
periods
3. High product concentration optimation
4. Instability of some production
5. Fewer technical difficulties
Any questions?