Foreword
Along with the development of biochemistry,cell physiology,
applied molecular biology,genetic engineering and metabolic
engineering,a great change in industrial fermentation is being
made from technique to science,Today when much account of
biotechnology has been made,it should be necessary to
reconsider,in the level of science,the breeding and
fermentation technology as a whole for industrial fermentation.
Based on the generalization and crystallization of the
researches in designing-breeding and fermentation technology,
and the research in teaching of fermentation principles and
microbial physiology,a presentation of the three viewpoints of
industrial fermentation,hereinbelow,was given at School of
Biotechnology,Wuxi University of Light Industry in 1997.
Three Basic Viewpoints of
Industrial Fermentation
Zhang Xingyuan
(Wuxi University of Light Industry,China)
E-mail,starxyz@public1.wx.js.cn
Abstract
Fermentation is the processes in which microbial
population functions,Those processes are supported and
maintained by the three kinds of flow,1,the electron flow
which operates along with energy-form transformation,2,the
metabolite fluxes which operate along with dissimilation and
assimilation,3,the information flow which operates along with
the metabolic regulations in different levels,On the basis of the
analysis of the operation rules of above three kinds of flow,the
three basic viewpoints of industrial fermentation are put
forward,1,the viewpoint of energy support,2,the viewpoint of
metabolic network,3,the viewpoint of cell economy,Those
viewpoints may reveal the biological attribution,the power and
potentiality of industrial fermentation,as well as the behavior
criterion of industrial fermentation.
Three basic viewpoints of
industrial fermentation
Part one
Three basic
View points of
industrial
fermentation
Part two
Basic
conceptions of
fermentation
principles
Part one,Three basic view
points of industrial
fermentation
? The viewpoint of energy support
—— Cell Energetics
? The viewpoint of metabolic network
—— Cell Second Anatomy
? The viewpoint of cell-economy
—— Cell-economy
1,The viewpoint of energy support
Microbial cells are the producers of the
target-products (or desirable products) for
industrial fermentation,It is necessary for
microbial cells’ growth and maintenance to be
supported by bioenergy,which should be
transformed by the apparatus of cells
themselves from energy sources of other types.
Thus,industrial fermentation manifests
biological attribute.
2,The viewpoint of metabolic network
There is neither absolute starting point nor
ultimate terminal point in metabolic network,
which consists of biochemical reaction
networks and trans-membrane steps,Any
intermediate metabolite in metabolic network,
or possibly the compound to be connected to
metabolic network by means of biology or
chemistry,would be developed into a target-
product or a starting material for industrial
fermentation.
3,The viewpoint of cell-economy
The economy systems of microbial cells have been
developing into competent economy in a long,long process of
inartificial selection,In the case of microbial breeding and
controlled fermentation,aiming at the production of target-
product,the metabolic flow should be regulated for earning
bioenergy on which the cells rely for living,and for the
accumulation of target-product or desirable products outside
cells; in that situation the state of cell-economy should be
oriented,The transformation from competitive-type economy
into guiding-type economy is dependent upon information-
guidance of the genetic and circumstance factors,nevertheless
the over-deviation from competent economy may bring down
on a crash of cell-economy.
Part two,Basic Conceptions
of Fermentation Principles
? Cell Energetics,1st to 4th items
—— the electron flow
? Cell second Anatomy,5th to 15th items
—— the substance (metabolite) flux
? Cell-economy,16th to 21st items
—— the information flow
Cell Energetics(1 to 4)
——the electron flow
1,Each microbial cell has its
own bioenergy
Being different from most animal cells
and most plant cells in the form of existence,
microbial cell is self-feeding and living
independently,Each microbial cell has its own
energy-transforming apparatus to get
bioenergy,Only supported directly by
bioenergy,the living cell can maintain a highly
ordered state.
2,Composition of Energy-
transforming Apparatus
Energy-transforming apparatus of
microbial cell includes enzymes in need of
being activated and their coenzymes,electron
transport chain and ATP enzyme in
cytoplasmic membrane of prokaryotic cell and
in inner-membrane of mitochondrion of
eukaryotic cell,as well as related carriers
which play auxiliary role in energy metabolism
and active transportation.
3,Electron Circuit in the
Metabolism of Microbial Cell
Chemo-organo heterotrophic microorganisms
are widely used in fermentation industry,They
transform chemical energy into bioenergy,which
can be used directly by organisms themselves,Bio-
oxidation in microorganism cells must be carried
out with the aid of coenzymes,Furthermore,both
respiration and active transportation are
accompanied by electron flow (or proton flow),
forming electron circuit in the metabolism of
microbial cell.
4,Biooxidation and Coenzyme
Regeneration
In living cells or their related inner-spaces,the
levels of the coenzymes of dehydrogenases,such as
NAD,that take part in biooxidation are constant,
thus the coenzymes must undergo regeneration and
recycle,Reduced coenzymes release electrons to the
electron-acceptors,at the same time undergo
regeneration,According to the categories of ultimate
electron-acceptors,biooxidation can be subdivided
into three types,aerobic respiration,anaerobic
respiration,and fermentation.
Cell Second Anatomy (5 to 15)
—— the substance flux
5,Biochemical Reaction
Pathway & Metabolic Pathways
Biochemical reaction pathway is
composed of a series of ordered
biochemical reactions,If the pathways
operate in a living cell,they are
referred to as metabolic pathways.
6,Biochemical Reaction Networks
& Metabolic Networks
According to the rules of biochemistry,
biochemical reaction pathways are integrated
into biochemical reaction networks; in other
words,the latter are the integration of the former.
According to the rules of metabolism,
metabolic pathways and trans-membrane
transport steps are integrated into metabolic
networks; in other words,the latter are the
integration of the former.
7,Making Interlinkage on
Metabolic Network
Metabolic intermediate compounds must be
found in metabolic networks,Although some of the
organic compounds can not be found directly in
metabolic networks,they may be linked up networks;
in other words,the metabolic networks of appointed
microorganism may be extended by interconnecting a
appointed compound to the networks with the
methods of chemistry or biology (include
recombinant DNA technology),thus,the metabolic
relationship between the organism and the
compounds would be made.
8,Metabolic Flux & Carbon Flux
Metabolic fluxes are operating when
metabolic material move along metabolic
pathways,In metabolic analysis for
industrial fermentation,the word
metabolic flux is quoted for the flux of
carbon-skeleton compounds.
9,Metabolic Mainstream
When metabolites flow,under certain
culture condition,within metabolic
network of microorganism,the metabolic
flux in which metabolites are relatively
concentrated is referred to as metabolic
mainstream of that condition.
10,Main Loading Pathway
The set of metabolic pathways
along which the metabolic mainstream
is running is defined as main loading
pathway,or loading pathway for short.
11,Variability and Selectivity
of Metabolic Mainstream
Metabolic mainstream of living microbial cell
is changing continuously,Changes may take place
in direction and flux of mainstream,even in
original loading pathway,Thus,the metabolic
mainstream of microorganism exhibits variability,
and the selectivity from the pathways within
metabolic networks,Both variability and
selectivity are based on heredity.
12,Ideal Loading Pathway
In the interest of product yield from main
raw material,it seems necessary that metabolic
mainstream flows through a presetting pathway,
in other words,metabolic intermediates are
relatively concentrated and flow through a
specifically preset loading pathway,The
presetting pathway is named ideal loading
pathway,This conception is derived from
loading pathway,and means a kind of virtual
loading pathway with subjective guidance
feature.
13,Problem of Mainstream
Matching with
In respect that metabolic mainstream
exhibits selectivity from the pathways
within metabolic networks,and the target
of industrial fermentation seems to let
metabolic mainstream flow through a
desirable loading pathway,thus the
problem of how to match mainstream with
ideal loading pathway is waiting for
working-out.
14,Five-section Pattern of Ideal
Loading Pathway
As a general rule in fermentation production,when a
population of microbial cells is cultivated in a medium,
nutrients outside cell cross over membrane enter cell,then a
target product forms with the help of three successive
sections of metabolic pathway,finally the target product
formed inside cell crosses over cell membrane and enters
the medium,Thus,the typical ideal loading pathway should
consist of five successive sections of metabolic pathways
bearing different metabolic tasks,The model mentioned
above is named,five-section pattern” of ideal loading
pathway.
15,Five-word Strategy for both
Breeding and Process Control
On the foundations of,five-section pattern”
of ideal loading pathway and metabolic
mainstream,setting out at the different angles
of view,the,five-word strategy” has been put
forward as charging-channelizing-withholding-
blockading-discharging,The strategy could be
used as a whole for both designed breeding and
fermentation process control.
Cell-economy (16 to 21)
——the information flow
16,Cell-economy & Cell-economy
Coefficient
A living cell of microorganisms is an open
system kept away from equilibrium,an economic
entity that governs the limited resources of energy
and material,The life process of a microbial cell is a
manipulating process of cell-economy,The total
effect of the process can be estimated upon
coefficient of cell-economy,which is the ratio of the
weight of cells produced to the weight of substrate
consumed.
17,Normal Metabolism &
Competitive-type Economy
In the struggle for survival,the orientation of evolution
for microorganisms is to develop the adaptability and to
improve the economy coefficient of cell manipulation process.
The wild-type strains,the survivor from the struggle for
survival,are rich in competitive power in the environment
they lived,In that environment,the distribution of metabolic
flux in metabolic networks and the situation of the
manipulating process of cell economy are favorable for cell
growth,propagate and get victory in the survival struggle.
Under the conditions mentioned above,the cell is in normal
metabolism state,the cell economy system exhibits features of
competitive-type economy.
18,Abnormal Metabolism &
Guiding-type Economy
The metabolic flow should be guided,provided the
accumulation of a metabolic intermediate outside cells is
desirable for production,Based on the information acquired
from metabolic analysis,applying the,five-word strategy”,it is
possible to design an ideal loading pathway and its
corresponding cultivation conditions and fermentation
technology,thereby to improve the producer and to modulate
the original process-control,Thus,the ideal result is that the
metabolic mainstream flows along the ideal loading pathway,It
is only when the cell is in abnormal metabolism state that the
cell economy system exhibits features of guiding-type economy.
19,Cell-economy is Restricted
Severely
The production of industrial fermentation relies
on the metabolism of microbial population,Although
cell economy of guiding-type is favorable for
producing specific metabolites,the conversion of cell
economy from competitive-type to guiding-type is
restricted severely by energy-metabolism,If the
running state of cell economic entities deviates
excessively from competitive-type economy,the
highly ordered state of cell will suffer from heavy
strike with the result of cell economy collapse.
20,Industrial Fermentation Directed
by Information Flow
In industrial fermentation,the microbial cells can
be regarded as bio-machines,which carry out energy-
metabolism and substance-metabolism,Likewise,the
microbial cell can be regarded as information
processor,which duplicates and transfers its own bio-
information,receives the physical,chemical,even bio
information outside and inside the cell; based on the
result of synthesizing those information flow,the cell
issues orders about metabolic regulation,thus,controls
the life process of itself.
21,Enigma of Restrictive Genetic
Information
It should be supposed that there must be
restrictive vital genetic information,which codes for
the basic metabolic networks and their regulation
mechanisms,in the genetic material of each cell,The
pieces of information are the root cause why
microbial cells can self-feeding and living
independently,and the inner-causes why the
adaptability of microorganisms is limited and why
the plans of designed breeding often cannot be
realize completely.
Conclusion
Industrial fermentation is speedily marching
towards science； fermentation engineering (or
microbiological bioengineering) is bound to be
the pioneer of biotechnology in the application
of bio-industrial production.
Thank you!
October 17,2000
Along with the development of biochemistry,cell physiology,
applied molecular biology,genetic engineering and metabolic
engineering,a great change in industrial fermentation is being
made from technique to science,Today when much account of
biotechnology has been made,it should be necessary to
reconsider,in the level of science,the breeding and
fermentation technology as a whole for industrial fermentation.
Based on the generalization and crystallization of the
researches in designing-breeding and fermentation technology,
and the research in teaching of fermentation principles and
microbial physiology,a presentation of the three viewpoints of
industrial fermentation,hereinbelow,was given at School of
Biotechnology,Wuxi University of Light Industry in 1997.
Three Basic Viewpoints of
Industrial Fermentation
Zhang Xingyuan
(Wuxi University of Light Industry,China)
E-mail,starxyz@public1.wx.js.cn
Abstract
Fermentation is the processes in which microbial
population functions,Those processes are supported and
maintained by the three kinds of flow,1,the electron flow
which operates along with energy-form transformation,2,the
metabolite fluxes which operate along with dissimilation and
assimilation,3,the information flow which operates along with
the metabolic regulations in different levels,On the basis of the
analysis of the operation rules of above three kinds of flow,the
three basic viewpoints of industrial fermentation are put
forward,1,the viewpoint of energy support,2,the viewpoint of
metabolic network,3,the viewpoint of cell economy,Those
viewpoints may reveal the biological attribution,the power and
potentiality of industrial fermentation,as well as the behavior
criterion of industrial fermentation.
Three basic viewpoints of
industrial fermentation
Part one
Three basic
View points of
industrial
fermentation
Part two
Basic
conceptions of
fermentation
principles
Part one,Three basic view
points of industrial
fermentation
? The viewpoint of energy support
—— Cell Energetics
? The viewpoint of metabolic network
—— Cell Second Anatomy
? The viewpoint of cell-economy
—— Cell-economy
1,The viewpoint of energy support
Microbial cells are the producers of the
target-products (or desirable products) for
industrial fermentation,It is necessary for
microbial cells’ growth and maintenance to be
supported by bioenergy,which should be
transformed by the apparatus of cells
themselves from energy sources of other types.
Thus,industrial fermentation manifests
biological attribute.
2,The viewpoint of metabolic network
There is neither absolute starting point nor
ultimate terminal point in metabolic network,
which consists of biochemical reaction
networks and trans-membrane steps,Any
intermediate metabolite in metabolic network,
or possibly the compound to be connected to
metabolic network by means of biology or
chemistry,would be developed into a target-
product or a starting material for industrial
fermentation.
3,The viewpoint of cell-economy
The economy systems of microbial cells have been
developing into competent economy in a long,long process of
inartificial selection,In the case of microbial breeding and
controlled fermentation,aiming at the production of target-
product,the metabolic flow should be regulated for earning
bioenergy on which the cells rely for living,and for the
accumulation of target-product or desirable products outside
cells; in that situation the state of cell-economy should be
oriented,The transformation from competitive-type economy
into guiding-type economy is dependent upon information-
guidance of the genetic and circumstance factors,nevertheless
the over-deviation from competent economy may bring down
on a crash of cell-economy.
Part two,Basic Conceptions
of Fermentation Principles
? Cell Energetics,1st to 4th items
—— the electron flow
? Cell second Anatomy,5th to 15th items
—— the substance (metabolite) flux
? Cell-economy,16th to 21st items
—— the information flow
Cell Energetics(1 to 4)
——the electron flow
1,Each microbial cell has its
own bioenergy
Being different from most animal cells
and most plant cells in the form of existence,
microbial cell is self-feeding and living
independently,Each microbial cell has its own
energy-transforming apparatus to get
bioenergy,Only supported directly by
bioenergy,the living cell can maintain a highly
ordered state.
2,Composition of Energy-
transforming Apparatus
Energy-transforming apparatus of
microbial cell includes enzymes in need of
being activated and their coenzymes,electron
transport chain and ATP enzyme in
cytoplasmic membrane of prokaryotic cell and
in inner-membrane of mitochondrion of
eukaryotic cell,as well as related carriers
which play auxiliary role in energy metabolism
and active transportation.
3,Electron Circuit in the
Metabolism of Microbial Cell
Chemo-organo heterotrophic microorganisms
are widely used in fermentation industry,They
transform chemical energy into bioenergy,which
can be used directly by organisms themselves,Bio-
oxidation in microorganism cells must be carried
out with the aid of coenzymes,Furthermore,both
respiration and active transportation are
accompanied by electron flow (or proton flow),
forming electron circuit in the metabolism of
microbial cell.
4,Biooxidation and Coenzyme
Regeneration
In living cells or their related inner-spaces,the
levels of the coenzymes of dehydrogenases,such as
NAD,that take part in biooxidation are constant,
thus the coenzymes must undergo regeneration and
recycle,Reduced coenzymes release electrons to the
electron-acceptors,at the same time undergo
regeneration,According to the categories of ultimate
electron-acceptors,biooxidation can be subdivided
into three types,aerobic respiration,anaerobic
respiration,and fermentation.
Cell Second Anatomy (5 to 15)
—— the substance flux
5,Biochemical Reaction
Pathway & Metabolic Pathways
Biochemical reaction pathway is
composed of a series of ordered
biochemical reactions,If the pathways
operate in a living cell,they are
referred to as metabolic pathways.
6,Biochemical Reaction Networks
& Metabolic Networks
According to the rules of biochemistry,
biochemical reaction pathways are integrated
into biochemical reaction networks; in other
words,the latter are the integration of the former.
According to the rules of metabolism,
metabolic pathways and trans-membrane
transport steps are integrated into metabolic
networks; in other words,the latter are the
integration of the former.
7,Making Interlinkage on
Metabolic Network
Metabolic intermediate compounds must be
found in metabolic networks,Although some of the
organic compounds can not be found directly in
metabolic networks,they may be linked up networks;
in other words,the metabolic networks of appointed
microorganism may be extended by interconnecting a
appointed compound to the networks with the
methods of chemistry or biology (include
recombinant DNA technology),thus,the metabolic
relationship between the organism and the
compounds would be made.
8,Metabolic Flux & Carbon Flux
Metabolic fluxes are operating when
metabolic material move along metabolic
pathways,In metabolic analysis for
industrial fermentation,the word
metabolic flux is quoted for the flux of
carbon-skeleton compounds.
9,Metabolic Mainstream
When metabolites flow,under certain
culture condition,within metabolic
network of microorganism,the metabolic
flux in which metabolites are relatively
concentrated is referred to as metabolic
mainstream of that condition.
10,Main Loading Pathway
The set of metabolic pathways
along which the metabolic mainstream
is running is defined as main loading
pathway,or loading pathway for short.
11,Variability and Selectivity
of Metabolic Mainstream
Metabolic mainstream of living microbial cell
is changing continuously,Changes may take place
in direction and flux of mainstream,even in
original loading pathway,Thus,the metabolic
mainstream of microorganism exhibits variability,
and the selectivity from the pathways within
metabolic networks,Both variability and
selectivity are based on heredity.
12,Ideal Loading Pathway
In the interest of product yield from main
raw material,it seems necessary that metabolic
mainstream flows through a presetting pathway,
in other words,metabolic intermediates are
relatively concentrated and flow through a
specifically preset loading pathway,The
presetting pathway is named ideal loading
pathway,This conception is derived from
loading pathway,and means a kind of virtual
loading pathway with subjective guidance
feature.
13,Problem of Mainstream
Matching with
In respect that metabolic mainstream
exhibits selectivity from the pathways
within metabolic networks,and the target
of industrial fermentation seems to let
metabolic mainstream flow through a
desirable loading pathway,thus the
problem of how to match mainstream with
ideal loading pathway is waiting for
working-out.
14,Five-section Pattern of Ideal
Loading Pathway
As a general rule in fermentation production,when a
population of microbial cells is cultivated in a medium,
nutrients outside cell cross over membrane enter cell,then a
target product forms with the help of three successive
sections of metabolic pathway,finally the target product
formed inside cell crosses over cell membrane and enters
the medium,Thus,the typical ideal loading pathway should
consist of five successive sections of metabolic pathways
bearing different metabolic tasks,The model mentioned
above is named,five-section pattern” of ideal loading
pathway.
15,Five-word Strategy for both
Breeding and Process Control
On the foundations of,five-section pattern”
of ideal loading pathway and metabolic
mainstream,setting out at the different angles
of view,the,five-word strategy” has been put
forward as charging-channelizing-withholding-
blockading-discharging,The strategy could be
used as a whole for both designed breeding and
fermentation process control.
Cell-economy (16 to 21)
——the information flow
16,Cell-economy & Cell-economy
Coefficient
A living cell of microorganisms is an open
system kept away from equilibrium,an economic
entity that governs the limited resources of energy
and material,The life process of a microbial cell is a
manipulating process of cell-economy,The total
effect of the process can be estimated upon
coefficient of cell-economy,which is the ratio of the
weight of cells produced to the weight of substrate
consumed.
17,Normal Metabolism &
Competitive-type Economy
In the struggle for survival,the orientation of evolution
for microorganisms is to develop the adaptability and to
improve the economy coefficient of cell manipulation process.
The wild-type strains,the survivor from the struggle for
survival,are rich in competitive power in the environment
they lived,In that environment,the distribution of metabolic
flux in metabolic networks and the situation of the
manipulating process of cell economy are favorable for cell
growth,propagate and get victory in the survival struggle.
Under the conditions mentioned above,the cell is in normal
metabolism state,the cell economy system exhibits features of
competitive-type economy.
18,Abnormal Metabolism &
Guiding-type Economy
The metabolic flow should be guided,provided the
accumulation of a metabolic intermediate outside cells is
desirable for production,Based on the information acquired
from metabolic analysis,applying the,five-word strategy”,it is
possible to design an ideal loading pathway and its
corresponding cultivation conditions and fermentation
technology,thereby to improve the producer and to modulate
the original process-control,Thus,the ideal result is that the
metabolic mainstream flows along the ideal loading pathway,It
is only when the cell is in abnormal metabolism state that the
cell economy system exhibits features of guiding-type economy.
19,Cell-economy is Restricted
Severely
The production of industrial fermentation relies
on the metabolism of microbial population,Although
cell economy of guiding-type is favorable for
producing specific metabolites,the conversion of cell
economy from competitive-type to guiding-type is
restricted severely by energy-metabolism,If the
running state of cell economic entities deviates
excessively from competitive-type economy,the
highly ordered state of cell will suffer from heavy
strike with the result of cell economy collapse.
20,Industrial Fermentation Directed
by Information Flow
In industrial fermentation,the microbial cells can
be regarded as bio-machines,which carry out energy-
metabolism and substance-metabolism,Likewise,the
microbial cell can be regarded as information
processor,which duplicates and transfers its own bio-
information,receives the physical,chemical,even bio
information outside and inside the cell; based on the
result of synthesizing those information flow,the cell
issues orders about metabolic regulation,thus,controls
the life process of itself.
21,Enigma of Restrictive Genetic
Information
It should be supposed that there must be
restrictive vital genetic information,which codes for
the basic metabolic networks and their regulation
mechanisms,in the genetic material of each cell,The
pieces of information are the root cause why
microbial cells can self-feeding and living
independently,and the inner-causes why the
adaptability of microorganisms is limited and why
the plans of designed breeding often cannot be
realize completely.
Conclusion
Industrial fermentation is speedily marching
towards science； fermentation engineering (or
microbiological bioengineering) is bound to be
the pioneer of biotechnology in the application
of bio-industrial production.
Thank you!
October 17,2000
