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

Disadvantages

Variable

Minimizing by-product
formation
Substrate converted to
biomass, product or both

Controlled by feedback
control
Requires accurate monitoring
and operator control

Continuous

Allow bioprocess to run

without operator control

Must have historical process

trend data

Intermittent

Allows feed to be fully utilised

before further addition
Reducing catabolite
repression

Controlled by feedback
control
Requires accurate monitoring
and operator control

Incremental

Allows feed to increase with

biomass formation
Optimizing growth rate and
product formation

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?