Industrial Microbiology and
Fermentation Technology
Textbook,Biology of Microorganisms
Seventh Edition
By Thomas D,Brock et al,(1996)
Website,http://www.prenhall.com/~brock
Lecturer,CHEN Guo-Qiang (陈国强 )
microbes@public3.bta.net.cn
Tel,62783844,Room 102,School of Life Sciences
Industrial Microbiology and
Fermentation Technology
? Industrial Microbiology is the discipline
that uses microorganisms,usually grown on
a large scale,to produce valuable
commercial products or carry out important
chemical transformations.
? Fermentation Technology is the technology
to grow cells in a large scale with high
efficiency,it also includes product recovery
processes.
Microbial products,microbial cells,enzymes,
pharmaceutical products
Specialty Chemicals and food additives
Flowsheet for developing an industrial
microbial fermentation process
? Strain selection
? Laboratory process development
? Pilot Scale up
? Industrial Scale up
? Downstream process development
? Product packaging techniques
? Other commercial consideration
? Examples
Strain Selection
–Purchase from Culture Collections
–Screening of nature circumstances
–Genetic engineering
–Mutations
–Cell biology techniques
International Culture Collections
Domestically,strains can be purchased from,CGMCC or
China General Microbiological Culture Collection Center
中国微生物菌种保藏管理委员会普通微生物中心,北京中关村
Screening of nature circumstances
Genetic
Engineering
Incorporation into
artificial plasmids of
genes from a wide
variety of sources has
made possible the
transfer of genetic
material across
virtually any species
barrier
Various high value
added products have
been produced from
the Genetic engineering
methods
Mutation
Via chemical
or physical,
and biological
means
Cell biology techniques
? Protoplast fusion (promote high
frequencies of genetic recombinants)
– removing the cell wall with lytic enzymes in
the presence of osmotic stabilizers.
– In the presence of fusogenic agent such as
polyethylene glycol (PEG),protoplasts are
induced to fuse and form transient hybrids
or diploids.
– Regeneration of viable cells from the fused
protoplasts.
Stages needed for transferring an industrial process
from the laboratory to the commercial fermentor
? Shake flash Experiments
? Lab scale fermentor (5-10 L)
? Pilot scale fermentor (300-3000 L)
? Commercial fermentor (10,000-500,000 L)
Laboratory process development
Shake Flask Experiments
Optimization of conditions
for cell growth and product
formation using shake flask
experiments:
1,pH
2,Temperature
3,Dissolved oxygen (DO)
4,Substrate choice
5,Maximal and optimal
substrate concentration
6,Others
Laboratory
Process
Development
Fermentor
Experiments
? Agitation
? Cooling and heating
? Air inlet and outlet
? pH control
? Nutrient addition
? Inoculation
? Viewing port
A series of fermentors used for
lab scale process development
Laboratory process development
Lab scale fermentor Experiments
? Batch process
? Fed-batch process
? Continuous process
? Semi-continuous
process
Fermentation Process,
Batch Process
? All the nutrients needed for cell growth will
only be added once at the beginning of
fermentation.
Fermentation process:
Fed-batch process
? During the fermentation,additional
nutrients will be added in a batch way to
promote the cell growth or product
formation and to avoid nutrient deficiency.
Fermentation process,Continuous process
Fermentation process,
Semi-continuous process
? Similar to continuous process,with
the addition of nutrients and outflow
of fermentation broth in a
continuous and batch way.
Process control and monitoring
? Process parameters to be monitors
Sugar consumption
pH
Temperature
Fermentation time (h)
Agitation
Cell Dry Weight
Product
Computer softwares have been developed to monitor and change the process on line
Pilot Scale Up
? Scale up,The transfer of a process from
small-scale laboratory equipment to large-
scale commercial equipment
? Pilot experiment
– To test the feasibility of the lab scale
fermentation process in a semi-industrial scale
– Pilot fermentors normally have a size ranging
from 100 L to 10,000 L,depending on the
products to be mass produced later.
Fermentor sizes for various purposes
Problems emerging during the scale up
? As the size of the equipment is increased,the surface-
volume ratio changes
? Large fermentor has much more volume for a given
surface area,it is obviously more difficult to mix the
big tank than the small flask
? In scale up studies on aerobic fermentations,oxygen
rate in the fermentor is best kept constant as the size
of the fermentor is increased.
– How to keep DO constant?
? Increase stirring rate
? Increase air pressure
? Use pure oxygen
? Increase air inlet
Industrial Scale up
? To transfer the pilot
scale results into a
commercially feasible
production setting.
? Fermentor sizes range
from 100 L to 500,000
L,depending on
products.
Industrial Fermentation Setting
Fermentation Technology
Textbook,Biology of Microorganisms
Seventh Edition
By Thomas D,Brock et al,(1996)
Website,http://www.prenhall.com/~brock
Lecturer,CHEN Guo-Qiang (陈国强 )
microbes@public3.bta.net.cn
Tel,62783844,Room 102,School of Life Sciences
Industrial Microbiology and
Fermentation Technology
? Industrial Microbiology is the discipline
that uses microorganisms,usually grown on
a large scale,to produce valuable
commercial products or carry out important
chemical transformations.
? Fermentation Technology is the technology
to grow cells in a large scale with high
efficiency,it also includes product recovery
processes.
Microbial products,microbial cells,enzymes,
pharmaceutical products
Specialty Chemicals and food additives
Flowsheet for developing an industrial
microbial fermentation process
? Strain selection
? Laboratory process development
? Pilot Scale up
? Industrial Scale up
? Downstream process development
? Product packaging techniques
? Other commercial consideration
? Examples
Strain Selection
–Purchase from Culture Collections
–Screening of nature circumstances
–Genetic engineering
–Mutations
–Cell biology techniques
International Culture Collections
Domestically,strains can be purchased from,CGMCC or
China General Microbiological Culture Collection Center
中国微生物菌种保藏管理委员会普通微生物中心,北京中关村
Screening of nature circumstances
Genetic
Engineering
Incorporation into
artificial plasmids of
genes from a wide
variety of sources has
made possible the
transfer of genetic
material across
virtually any species
barrier
Various high value
added products have
been produced from
the Genetic engineering
methods
Mutation
Via chemical
or physical,
and biological
means
Cell biology techniques
? Protoplast fusion (promote high
frequencies of genetic recombinants)
– removing the cell wall with lytic enzymes in
the presence of osmotic stabilizers.
– In the presence of fusogenic agent such as
polyethylene glycol (PEG),protoplasts are
induced to fuse and form transient hybrids
or diploids.
– Regeneration of viable cells from the fused
protoplasts.
Stages needed for transferring an industrial process
from the laboratory to the commercial fermentor
? Shake flash Experiments
? Lab scale fermentor (5-10 L)
? Pilot scale fermentor (300-3000 L)
? Commercial fermentor (10,000-500,000 L)
Laboratory process development
Shake Flask Experiments
Optimization of conditions
for cell growth and product
formation using shake flask
experiments:
1,pH
2,Temperature
3,Dissolved oxygen (DO)
4,Substrate choice
5,Maximal and optimal
substrate concentration
6,Others
Laboratory
Process
Development
Fermentor
Experiments
? Agitation
? Cooling and heating
? Air inlet and outlet
? pH control
? Nutrient addition
? Inoculation
? Viewing port
A series of fermentors used for
lab scale process development
Laboratory process development
Lab scale fermentor Experiments
? Batch process
? Fed-batch process
? Continuous process
? Semi-continuous
process
Fermentation Process,
Batch Process
? All the nutrients needed for cell growth will
only be added once at the beginning of
fermentation.
Fermentation process:
Fed-batch process
? During the fermentation,additional
nutrients will be added in a batch way to
promote the cell growth or product
formation and to avoid nutrient deficiency.
Fermentation process,Continuous process
Fermentation process,
Semi-continuous process
? Similar to continuous process,with
the addition of nutrients and outflow
of fermentation broth in a
continuous and batch way.
Process control and monitoring
? Process parameters to be monitors
Sugar consumption
pH
Temperature
Fermentation time (h)
Agitation
Cell Dry Weight
Product
Computer softwares have been developed to monitor and change the process on line
Pilot Scale Up
? Scale up,The transfer of a process from
small-scale laboratory equipment to large-
scale commercial equipment
? Pilot experiment
– To test the feasibility of the lab scale
fermentation process in a semi-industrial scale
– Pilot fermentors normally have a size ranging
from 100 L to 10,000 L,depending on the
products to be mass produced later.
Fermentor sizes for various purposes
Problems emerging during the scale up
? As the size of the equipment is increased,the surface-
volume ratio changes
? Large fermentor has much more volume for a given
surface area,it is obviously more difficult to mix the
big tank than the small flask
? In scale up studies on aerobic fermentations,oxygen
rate in the fermentor is best kept constant as the size
of the fermentor is increased.
– How to keep DO constant?
? Increase stirring rate
? Increase air pressure
? Use pure oxygen
? Increase air inlet
Industrial Scale up
? To transfer the pilot
scale results into a
commercially feasible
production setting.
? Fermentor sizes range
from 100 L to 500,000
L,depending on
products.
Industrial Fermentation Setting