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Microbiologia Industrial

Fundamentos

Resumo do processo de fermentao


Processo a montante
Fermentao de materiais crus

Produo de microrganismos

fermentao
Processo a jusante
Purificao do produto

Effluente (lixo)

PRODUTO

Processo a montante USP


A produo do microrganismo
O meio de fermentao
A fermentao

Processo a jusante DSP


Recolha das clulas
Rompimento das clulas
Purificao do produto ( a partir das clulas
ou do meio)
Passos finais

Crescimento microbiano
Matemtica do crescimento batch
E sistema semi-continuo

Quando, durante o ciclo de crescimento, o produto


til industrialmente produzido?

Metabolitos primrios

Substrato para
crescimento

clulas

lcool

acar

Clulas

Metabolito primrio
O crescimento s ocorre com produo de energia,
a produo de etanol ocorre em paralelo

Metabolitos secundrios
Substrato para
crescimento
clulas
Penicilina

Clulas
Metabolito
secundrio

Metabolito
primrio
acar

Aps o crescimento celular, o metabolito secundrio produzido a


partir do primrio ou de substrato

Caractersticas dos metabolitos secundrios


1. So formados por relativamente poucos organismos
2. No so essenciais para o crescimento
3. A sua formao extremamente dependente das condies
de cultivo composio do meio de cultivo
4. Pode ocorrer represso da produo
5. Por vezes so produzidos como um grupo de estruturas
relacionadas - 30 antraciclinas diferentes
6. Podem ser produzidos em demasia overproduction
7. Se forem produzidos a partir de metabolitos primrios
podem vir de vrios produtos intermedirios que
acumulam no meio ou nas clulas

Curva de crescimento batch


(crescimento descontinuo)

estacionria

Curva de crescimento para uma populao


microbiana em cultura batch
Fase lag: no ocorre crescimento exponencial. Visvel se as
clulas tiverem de fazer adaptaes
Fase exponencial: cada clula d origem a duas clulas. A
taxa de crescimento exponencial influenciada pelas
condies ambientais (g=20min 48h 4000xpeso da terra)
Fase estacionria: no existe variao net no nmero de
clulas. Continuam os processos biosintticos. Activao
de um pull gentico especfico genes sur
Fase de morte: pode ocorrer lise ou no.

Crescimento microbiano
Crescimento = aumento do nmero de clulas numa
populao ou da massa
Taxa de crescimento = modificao do nmero de clulas
(ou massa) por unidade de tempo
Tempo de gerao = o tempo necessrio para uma clula
dar origem a duas (duplicar a populao)
Taxa de crescimento no tempo x = proporcional ao nmero
de clulas (ou massa) presente nesse tempo
Crescimento exponencial = quando o nmero de clulas
duplica a cada unidade de tempo esto em crescimento
balanceado

Crescimento exponencial
dX =X
dt

Taxa de crescimento instantnea

lnX=lnX0+ (t)

Descreve a fase exponencial

X=X0e (t)

Prever a densidade populacional

g= ln 2 = 0.693

Tempo de gerao

Taxa de crescimento (valor mdio)

k=1
g

=0.693k

Operao batch

1. produce biomass
2. produce primary
metabolites
3. produce
secondary
metabolites

Fase curta de produo mxima de produto

Limitaes ao crescimento
Can be explored by growing the organism in the
presence of different initial substrate concentrations
and plotting the mass concentration at stationary phase
against the initial substrate concentration.
x = Y(SR-s)

(3)

x
[biomass] produced
Y
rendimento (g biomass produced g-1
substrato consumido)
SR
initial substrate concentration, and
s
residual substrate concentration

Concentrao inicial de substrato

Concentrao de biomassa
na fase estacionria

The decrease in growth rate and the cessation of growth, due to


depletion of substrate may be described

= max s/(Ks + s)
s

is the residual substrate


concentration

Ks
is the substrate utilization
constant ( is a measure of the affinity
of the organism for its substrate)

is the specific growth rate

S when = max/2

Cintica de Monod

max

Ks

Estimating Monod Model parameters


A Lineweaver Burke transformation of the Monod Model is:

Since at steady state, = D, equation 58 can be rewritten as:


The Monod model parameters can thus be determined from a plot of 1/D versus 1/S (Figure 18).

O grfico mostra com pode ser calculado:

o m taxa especifica
de crescimento
maxima
E a Ks constante de
utilizao do
substrato

Formao de produtos ligados ao crescimento


dp/dt = qpx (5)
p concentrao do produto
qp taxa especifica de formao do produto (mg
product g-1 biomass h-1)

Product formation is also related to biomass


production:

Yp/x
biomass)

dp/dx = Yp/x
(6)
rendimento do produto (g product g-1

Multiply equation (6) by dx/dt, then:

dx/dt dp/dx = Yp/x dx/dt


dp/dt = Yp/x dx/dt
But from equation (1), dx/dt = x, and therefore:
dp/dt = Yp/x x,
and we know from equation (5) that dp/dt = qpx
and therefore:
qpx = Yp/x x
qp = Yp/x
(7)

qp taxa especifica de formao do produto (mg product


g-1 biomass h-1)
Yp/x redimento (g de produto por g de biomassa
produzida)

Produtos independentes do crescimento


Produced under certain physiological
conditions (usually in stationary phase)
Typical examples are antibiotics and
proteinases

Fed-Batch Fermentation
Operao semi-continua

Generally, Fed-Batch fermentations require greater monitoring and


control than batch fermentations.

In Fed-Batch Fermentation substrate is added in increments at various


times throughout the course of the reaction. These additions prolong
both the log and stationary phase and thereby increase the biomass and
the amount of synthesis of stationary phase metabolites such as
antibiotics.

Microorganisms in the stationary phase often produce proteolytic


enzymes, which will attack any protein product synthesized by a
genetically engineered microorganism. Therefore, when producing
proteins from a recombinant microorganism, it is important to prevent
the fermentation reaction from reaching this part of the growth cycle.

There exists several feed-strategies:


1.

Addition of growth medium Increase in


volume

2.

Addition of the limiting substrate


in volume

3.

Addition of the limiting substrate (concentrated


solution) and in slow rate
Slight increase in
volume

4.

Addition of a very concentrated solution of the


limiting substrate at very slow rate
Insignificant increase in volume

Increase

5. Another fed-batch type is cyclic fed-batch culture:


Dilution of the culture by withdrawing a portion of the
culture and using the residual culture as starting point
for a further fed-batch process (variable volume).
This will lead to periodic shift-up in growth-rate followed
by a gradual shift-down.
Dilution of the culture can also be achieved by
withdrawing culture and refilling to original level with
dH2O or medium NOT containing the feed substrate
(fixed volume).

= specific growth rate


x = biomass concentration
S(GLS) = growth limiting
substrate
SN = any other Substrate
than S (GLS)

Fed batch reactors are thus


primarily used for producing
Products under low
nutrient or substrate conditions.

Biomassa

Volume
D=F/V
D=taxa de diluio h-1,
F=fluxo(L/h)
V=volume do reactor (L)

Substrato

Produto

Homeostasia a manuteno da
integridade intracelular
pH baixo, presena de substancias
txicas e a acumulao de produtos do
metabolismo levam reduo do
rendimento em biomassa
O ATP direcionado para o transporte
activo de substancias =
desacoplamento metablico

Aplicaes do sistema fed-batch

the substrate is inhibitory and thus low substrate levels must be maintained or
the cells will be inhibited. For example:
Vinegar Production
Amylase Production

the product or biomass yields are highest at low substrate


concentrations. For example:
Mammalian Cell Systems
Bakers Yeast Production
Antibiotic Production

product formation is dependent on a specific nutrient composition, eg.


a specific carbon: nitrogen ratio

A fed-batch culture in essence


is a batch culture which is
supplied with either fresh
nutrients (e.g. growth-limiting
substrates) or additives (e.g.
precursors to products).

http://userpages.umbc.edu/~gferre1/outline.html

Amylase production
Amylases are produced by fungi and bacteria from a starch
based medium. High levels of starch will increase the
medium viscosity and thus decrease mass transfer rates and
increase agitation costs.

High [starch]
High medium viscosity
Low mass transfer rates
High energy consumption

Low [starch]
Lower medium viscosity
Higher mass transfer rates
Lower energy consumption

Vinegar production
The main flavouring component of vinegar is acetic acid. The acetic acid is produced from
the oxidation of ethanol:
Ethanol is more toxic to cells than the acetic and pH.
In fact the acetic acid bacteria are able to metabolize at pH values of less than 3 and can
produce up to 180 g.l-1 of acetic acid.
Under these conditions however, ethanol concentrations of less than 2%w/v will inhibit the
cells. By slowly adding the alcohol with a fed-batch reactor, low ethanol concentrations can
be maintained in the reactor.

High [ethanol]
Low [ethanol]
Inhibition of cell growth
Low acetic acid yields
High acetic acid yields

Ethanol is typically added as 96% w/w ethanol, but boutique vinegars are made from
port or rice wines. The lower alcohol concentration in the feed, then the greater will be
the dilution of the final product, due to the higher water content entering the reactor.
Thus the use of 96% w/w ethanol is preferred.

As the acetic acid accumulates and the pH falls, cell growth ceases and acetic
acid production becomes non-growth associated. The process therefore cannot
be performed in a continuous reactor as they would be washed out.

Vinegar is typically produced in fed batch reactors because


a. a fed batch reactor can be used to maintain low acetic acid concentrations
b. a fed batch reactor can be used to maintain low ethanol concentrations
c. acetic acid bacteria tend to ferment at high ethanol concentrations
d. All of the above are correct.

Mammalian cell culture


Mammalian cells are subject to the Crabtree effect. That is under high glucose
concentrations, they will ferment rather than respire.
Many cell culture media contain up to 4 g.l-1 of glucose. In batch culture systems, the
cells will ferment in these media. As a result, high lactate and low biomass yields will
arise. In large scale mammalian cell culture, fed batch reactors are used.
With fed batch reactors, the medium is added slowly to the culture. The resultant low
glucose concentrations cause the cells respire instead of ferment. This leads to the
production of high biomass and desired product yields.
High [glucose]
High lactate yields
Low biomass yields
Low product yields

Low [glucose]
Low lactate yields
High biomass yields
High product yields

Monoclonal antibodies are typically produced in fed batch reactors because


a. hybridoma cells respire at high glucose concentrations
b. hybridoma cells ferment at low glucose concentrations
c. hybridoma cells produce higher lactate yields at high glucose concentrations
d. All of the above are correct

Baker's yeast production


Baker's yeast ( Saccharomyces cerevisiae) is an important commodity. Large scale
production of baker's yeast is performed in fed-batch reactors using a medium based on
glucose or sucrose. Saccharomyces cerevisiae is subject to the Crabtree effect. High
glucose or sucrose concentrations will cause the cells to ferment rather than respire.
To increase the profitability of yeast production, fed-batch reactors are used.
The feed to the fed batch reactors can contain more than 200 g.l-1 of sugar. However, as
long as the feed flow rate is not too high and sufficient oxygen is available, low sugar and
high biomass yields can be achieved.
Baker's yeast can also be produced in continuous cultures. However fed-batch reactors are
preferred due to the problems that contamination can cause in continuous cultures.
High [sugar]
High ethanol yields
Low biomass yields

Low [sugar]
Low ethanol yields
High biomass yields

Yeast biomass is typically produced in fed batch reactors because


1. yeast cells respire at low glucose concentrations
2. yeast cells ferment at low glucose concentrations
3. yeast cells produce ethanol at low glucose concentrations
4. All of the above are correct

Antibiotic production
Most microbial derived antibiotics such as penicillin and cephalosporins are produced in a
two stage process. In the first stage, the cells are grown in a batch manner. After the
biomass concentration has reached a maximum, the process is switched to a fed-batch
mode.
The reason for this is that in general, antibiotic production occurs maximally when cell
growth is very slow or ceases.
By using a fed-batch reactor, substrates and nutrients can be supplied at a slow rate in
quantities sufficient for antibiotic formation and cell maintenance but insufficient to
promote high cell growth rates. This in effect "extends the stationary phase".
No extension of stationary phase
Low antibiotic yields

Extension of stationary phase


High antibiotic yields

Antibiotics are typically produced in fed batch reactors because


a. antibiotic yields are generally lower when cells enter the stationary phase
b. the precursors are often toxic to the cells
c. antibiotic yields are generally higher when cell growth slows and extension
of stationary phase can be maintained.
d. All of the above are correct.

Crescimento em fermentador
Matemtica do crescimento em
fermentador

Cultura continua
um sistema aberto, de volume constante
ao qual meio adicionado constantemente e
de onde continuamente removido lquido
Constantes quando em equilbrio:
Nmero de clulas
Estado do nutriente (meio)
Steady State

O fermentador
Taxa de diluio
Concentrao do nutriente limitante
Controlo independente da taxa de
crescimento e da taxa de produo
Taxa de crescimento taxa de diluio
Taxa de produo concentrao do nutriente
limitante

Urina de cavalo

O conceito de cultura continua


existe desde o sculo XIX.
Monod foi o primeiro a analizar
a cultura continua criando o
modelo

Grande aplicao no tratamento de guas pouca na industria de


fermentao

Where
X is the concentration of biomass in the fermenter and effluent
S is the concentration of substrate in the fermenter and effluent
P is the concentration of product in the fermenter and effluent
Xo is the concentration of biomass in the fermenter and effluent
So is the concentration of substrate in the fermenter and effluent
Po is the concentration of product in the fermenter and effluent
F is the feed and effluent flow rate
V is the liquid volume in the fermenter

Fermentador continuo mais comum: quimostato


Volume constante

Pode-se escolher outra varivel para manter constante: pH, turbidez


Volume varivel e fluxo varivel

Energia de manuteno = quantidade


mnima de energia necessria para manter a
estrutura e a integridade celular.

Aplicaes da fermentao continua


Contaminao no tem
significado
Os volumes que entram no
so possveis de sustentar num
sistema batch

Reactor industrial continuo com


1 milho de litros
Produo de biomassa bacteriana
para extrao de protena para
uso animal (Pruteen)

Taxa de diluio e tempo de residencia

Matemtica do crescimento em fermentador


O crescimento bacteriano uma funo da concentrao de nutriente
max = taxa de crescimento
com saturao de nutriente
= max

S
Ks+S

S = concentrao do nutriente limitante


Ks = constante de saturao quando = 1 max
2

max e Ks podem ser estimados num grfico colocando


1/ no eixo dos y e 1/ S no eixo dos x.
O valor de intercepo do eixo dos y o valor de 1/ max

Taxa especfica de crescimento

max

1/2max

Ks

Concentrao de substrato

Reactor de mistura perfeita


a concentrao dos componentes no reactor encontra-se
igualmente distribuda pelo lquido do reactor

No existe porque:
necessrio tempo para mover as
substncias
Em grandes reactores existem zonas
mortas sem mistura

So sistemas quadrados
Cultivo de clulas

Fluxo de banda perfeita


O fluxo de lquido passa como uma rolha ou banda pelo reactor.
No h mistura e existe um gradiente de concentrao entre o
ponto de entrada do lquido e o ponto de sada

No existe porque:
Existe sempre difuso

So sistemas mais
longos que largos
Produo de enzimas

Populao constante concentrao de nutrientes perto de 0


a adio de nutriente influencia a taxa de crescimento

Taxa de diluio D = F
V
Em equilbrio = D

F = taxa de fluxo L/h


V = volume fermentador
porque D controla a quantidade de S

Quando a concentrao de substrato (S) baixa,


a taxa de crescimento () uma funo directa de S
S depende em qualquer momento da taxa de diluio (D)

Densidade populacional pode ser definida como uma relao


entre o crescimento celular e o consumo de nutrientes
Y= dX
dS

Y= peso de bactrias formado


peso de substrato consumido

uma medida de eficincia

rendimento

Quando o fermentador inoculado com um pequeno nmero


de clulas e a taxa de diluio no excede o valor crtico
(Dc) o nmero de organismos comea a aumentar

dX = X DX
dt

dX = crescimento sada
dt

Inicialmente > D e dx/dt positivo


medida que a populao aumenta decresce
Se D for mantido constante no equilbrio = D e dX/dt = 0
Steady state

O equilbrio possvel se a taxa de diluio no exceder Dc


Dc depende da concentrao no reservatrio do substrato limitante (Sr)
Dc = max ( Sr )
Ks + Sr
Se Sr > > Ks
no equilbrio obtm-se taxas de crescimento perto de max

dS = entrada sada consumo


dt

dS = Sr D SD X
dt
Y

No equilbrio (steady state):


dS/dt = 0
X = Yxs (Sr S)

X=concentrao do organismos

S = Ks (
D )
max - D
Estas equaes tm as constantes Sr, Y, Ks e max.
Uma vez conhecidos os seus valores, os valores de X e S podem
ser calculados para qualquer taxa de diluio

If you want the organisms to grow at a


faster rate, increase the dilution rate.
If you want the organisms to grow at a
slower rate, decrease the dilution rate.
Optimization of product and biomass
formation can therefore be performed by
setting the correct dilution rate.

As equaes prevm que em


condies de equilibrio

Em equilibrio

Concentrao do produto no fermentador em equilibrio


em equilibrio

Se = D

Monod model
Estas equaes aplicam-se apenas ao clculo de produtos associados ao
crescimento

Matemtica do crescimento

=taxa especfica de crescimento


Y=coeficiente de produo de biomassa
S=concentrao de substrato
D=taxa de diluio
D=Volume entra/Volume reactor

Sumario da Fermentao em Cultura Continua


Hydraulics

Tempo de residencia

Mass balance Equations

Steady-state Equations

=D

Washout
X

New steady state

=D

The dilution rate in a chemostat must be less than the


the critical dilution rate.

Processo de fermentao
Fermentadores

Processo de fermentao
Solid-sate fermentation (proc. Koji)
Difcil controlo de contaminao; temperatura;
arejamento; humidade

Uso de fermentadores (bioreactores)


Controlo computadorizado de pH; temperatura;
concentrao do oxignio dissolvido; taxa de
tomada de O2; taxa de evoluo de CO2,
arejamento; presso; espuma; agitao.
Densidade celular mantida

Fermentao em suporte slido


Os microrganismos crescem em substratos slidos
porosos, na ausncia de gua livre.O crescimento e
o produto secretado ocorrem tanto na superfcie
como no interior do suporte.
Substratos de suporte: trigo, gro para cerveja,
casca de arroz, polpa de beterraba, bagao.
A maioria emprega fungos (no formam esporos
quando submersos).
Produo de proteases, lipases, celulases e
oxidases.
Queijos, sufu, cogumelos

Bioreactores
Tanque com agitao (impeller)
o mais utilizado.
adequado para:
fermentaes que envolvam miclio de fungo
Bio-polimeros de elevada viscosidade

Coluna de bolha (sparger)


A agitao e o arejamento feito por um
difusor de fundo, com bocas distribudas
uniformemente ao longo de uma seco, em
anel, em tubos paralelos ou em estrela

Factores ambientais que afectam o


crescimento

Temperatura
Destruio trmica
Refrigerao
Actividade da gua
Actividade da gua
Potencial redox
Radiao
Presso hidrosttica
Controlo de microorganismos

temperatura

Temperatura mnima
Temperatura ptima
Acima da temperatura ptima
Coeficiente de temperatura = relao entre
o aumento da velocidade de reaco e a
temperatura
1.5 a 2.5 por cada 10C

Destruio trmica
Segue uma cintica exponencial

D = tempo necessrio para que o nmero de


sobreviventes caia 10% do valor inicial (minutos)

D indicaba el tiempo necesario para lograr que el


nmero de supervivientes se redujera al 10% de la
poblacin inicial, el valor z indica el incremento en la
temperatura (medida en nmero de grados) necesario
para que el valor D se reduzca a la dcima parte del
inicial.

Actividade da gua
actividad de agua a la relacin entre la
presin de vapor de agua del substrato de
cultivo (P) y la presin de vapor de agua
del agua pura (P0)
El valor de la actividad de agua nos da una
idea de la cantidad de agua disponible
metablicamente

Scale-up

Scale-up
= transferir o processo de uma escala de laboratrio
para uma escala industrial

Parmetros essenciais
Energia, O2 temperatura

Funo do engenheiro bioqumico

Processo de scale-up
1. Experincias em batch
2. Fermentador de laboratrio (1-10L)

Testam-se: variaes do meio, temperatura,


pH.

3. Estgio piloto em fbrica

Condies similares s do laboratrio

4. Fermentador comercial (10000-500000L)

A extrapolao (scale-up)

O processo de trabalho que permite passar de uma escala de laboratrio ou


piloto de desenvolvimento, para uma escala ampliada de produo.
tambm um mecanismo de seleo de equipamentos e de condies de
operao industrial, mas cuja construo obedece a regras de ordem social,
_pol1tica e tcnica.
A necessidade da abordagem emp1rica da extrapolao demonstrada sob o
ponto de vista da teoria da similaridade de sistemas e do conceito de
aplicabilidade da teoria geral a problemas especficos, estes defin1veis por
condies de contorno emp1ricas. So apontadas tipos de incertezas
envolvidas na extrapolao, e a falta de dados sobre esta, agravada pelo baixo
nvel de informao contido em patentes. mostrado o processo de trabalho
de inovao na qumica industrial e sugerido que a experimentao-piloto
constitui um paradigma metodolgico desta.
A heterogeneidade dos sistemas tecnolgicos, a sinuosidade do processo
decisrio e a incorporao da subjetividade do trabalho sob a forma de regras
heursticas incorpora a histria do processo de P&D na prescrio do objecto
extrapolado.

SCALE-UP CONSIDERATIONS

This process is the important step for transferring bench-top fermentations


to mass production. Scale-up would be very simple if all parameters
affecting bacteria remained the same. Numerous empirical and semiempirical relationships are often used to correlate variables such as shear
rates and oxygen mass transfer with physical parameters such as impeller
speed and reactor dimensions. One of the most important and often
overlooked factors in scale-up is power consumption. When scaling-up a
process, it is important to factor in the power costs of operating large
fermenters.

SIMPLIFY PROCESS SCALE-UP


The Advantage Series 4100 process scale-up reactor for
pharmaceutical compound development simplifies scale-up work by
allowing chemists to program and control reaction conditions such as

temperature, reagent addition amounts and rates, and


stirring speed using a single computer running CamileTG
software (Figure 1).Using the Advantage Series multiple-parameter
recipe editor, chemists can program the Advantage Series 4100 reactor
to use real-time feedback from analytical instrumentation to
automatically obtain optimum conditions for the formation of desired
compounds, increasing yield and making more efficient use of time
and materials
The CamileTG software application for the 4100 reactor automatically
creates a chronological record of each reaction that correlates
analytical data with the reaction recipe as the reaction progresses
. These records provide chemists the detailed process information
needed to troubleshoot difficult scale-up reactions, increase margins of
safety, or adjust the reaction recipe to
increase yield.Reaction recipes can be saved and re-used to exactly
reproduce reaction conditions on the same equipment or on similarly
configured 4100 reactors at different locations.
SIMPLIFY PROCESS SCALE-UP
Figure 1: The Advantage Series 4100 process scale-up reactor
utilizes CamileTG software, a flexible design platform created
specifically for process laboratory automation.

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Processo a jusante (Downstream) DSP

Resumo do processo de fermentao


Processo a montante
Fermentao de materiais crus

Produo de microrganismos

fermentao
Processo a jusante
Purificao do produto

Effluente (lixo)

PRODUTO

DSP=abarca todo o processo a seguir


fermentao
Objectivo:

Eficincia
Reproducibilidade
Recuperao em segurana
Maximizao da quantidade
Minimizao dos custos do produto alvo

Factores da fermentao que afectam o


DSP
Propriedades dos microorganismos:
Morfologia
Floculao
Tamanho
Rigidez da parede

Estes factores afectam:


Filterabilidade
Sedimentao
Eficincia da homogeneizao

Bioseparaes
Recuperao e purificao de protnas e produtos de fluidos
so uma percentagem relevante do custo de produo:
10 a 80% entre alimentos/aditivos e enzimas terapeuticas
Trs categorias :
Alta produtividade - baixa resoluo
Baixa produtividade alta resoluo
Alta produtividade alta resoluo
Esquema de separao normal: RIPP
Remoo, Isolamento, Purificao e Polimento

Requerimentos para a bioseparao

Reduo do volume
Concentrao por enriquecimento
Remoo de impurezas especficas
Preveno da catalise
Recomendaes especficas (farmacolgicas)
Aumento da estabilidade proteica
Reduo da proteolisis

Caracteristicas da protenas
Os produtos esto presentes em baixas quantidades
Presentes com um nmero elevado de impurezas algumas
muito semelhantes
So termolabil
So senciveis a condies como pH e sal
So senciveis a substancias qumicas como solventes e
surfactantes
Normalmente os produtos tm de ter elevada qualidade
Implica condies de separao eficientes mas muito
suaves

3-sedimentao

1. Utilizados sobretudo na produo de bebidas alcolicas


2. S para grandes floculos (100m)
3. Diferenas de densidade entre o meio e a particula tm
de ser grandes (Stokes)

ADVANTAGES OF CENTRIFUGATION OVER FILTRATION


Of the two technologies commonly used to separate fluids,
centrifugation and filtration, CEPA centrifuges offer these
benefits:
1.
2.
3.
4.
5.

Economical to use, no costly membranes or other disposables.


Faster; In the same floor or bench space, CEPAs process many
times faster than filtration systems.
No wasted product; with CEPA High Speed Centrifuges,
separated solid and liquid components are readily available.
Filtration systems trap and embed cell mass and other solids.
Consistent performance; No mid-run degradation as filters clog.
No membrane aging or lot variations. No chemical leaching from
polymeric filters.
Rugged; Heavy duty construction. All stainless steel* fluid path
resists chemicals and high temperatures.

Aula 7
Produo industrial de penicilinas e
tetraciclinas

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