Praceadings of I'{enotiahol ConfeEn e on chehtical an l Biopn.es E\iaceting
Uniwrsiti Malqria Sabah Kotu Kintua l
27'
2q A4u!2003,
Modellingand Anatysisof DynamicBehaviourof a Fed'batchPenicillin
Mathematical
G FermentationProcess
Arshad Ahmadl Noor Asma Fazli Abdul Samad2Chow Ai Wei:
'Depdrtment aJ chenical Engi@enng
Unireniti Teknalosi Malarsia, 8 13 10 UTM Skudai,Jahoa Mata)sia
TeL +6A-7 553-5610Far: +60'7'558'1463,Enait: a\hdd@fl<kba-utmmv
'1lnboruko' oJPrccessContnl, Depadnent of Chenical EngikeetnLs
Uin'e rcili TeLrola|i M.tlalsia, 8 13 10 UTM Skudai,Johot, MaLalsia
Tel: +60-7 553 5858.Enail: asnafazli@hotnail.comai|u chaw@vth.'o.con1
Abstract
This paper .liscussesthe charucteristicsaJ Peni.illin C
ferhlentations wilh subslrute inhibition using d)hanic
simuLatiott. The feffientation Ptocess tras situuLated in
aM anab'se' of the dYatuic
MATIAB e innftett
behariaut ol the pncess \|ere carried out to pnti.le the
necetturypncess insiShts.Dltami( sinuLdtiotlsrereated
raridtians in the sensitiriry oJ the tnodeLto subsiate
concnttutiors, dependinqon the operctiry poi l This
vaiation indicates non-lineatit! in d)nanic behaviour PID
co rol was ako ewluate.l dnd resuht are deftonstruted
Keywords:
In this work, we concenlmleon the developmentol a
completemathematicalmodel and sinulation test-bedfor
processcontrol studies on a Penicillin G fennentalion
process.
The mechanisticmodelofBajpai andReuol1l, and
the extendedmodel by Biml et al.[2] were ulilized as the
basisofourmodellingeffons.Thesemodelsareclassifiedas
unstruclured model and they are simpler than slruclured
models. In unstruclurcdmodels, all cellular physiology
;nformationis galheredin a singlebiomas termso that$ere
is no explicit strudural information abolt the ceuular
aclivity t2l. On the othe. hand, slructured models for
penicillin-pmducdon
includethe effectsof cell physiology
on penicillinproduction.
Mathematical Modelling
Peniciuin Gi Femenlation; Dynamic simulaiioni PID
MalhematicalModellingof Penicillin Fermenlation
Introduction
In a fed-batchoperation,there is no removalof producls
f.om the fermenteruntil the end of the process.The outpu!
of a fermenterduring penicillin produclion. fd. is therefore
equal to zerc Gee Eqlation (l)). The nutrienb arc fed at a
variablerateto thecullurebroth in a fed-balchprocessI7l.
as a secondary
Penicjllinis an anlibioticthat is categorised
menbolite product thar hs played impo.tant roles
'n
pharmaceudcal field for years. Genemlly. fte industrial
prodDctionof penicillin is characlerisedby two dislinct
regim€s.The initialphaseis lo grow cellsin a batchculture.
Thh is $en followed by a fed-batch operalion ro promote the
b;osynthesis
ofpenicillin. ln fermenlation,substrateis very
impo.lanl for cell growft. mainGnanceof the microbial
population and fo.malion of products. Howevea for some
prccesses.prcduct fo.mations may be suppressedwhen
subskaleconcenlradonexceedscertainvalue. As a result,
conlrolledsupplyofsubstrateis nec€ssary.
ln order to explore fte effect! of process variables and
analysethe sensitivilyof thesevariables,the useofdynamic
This has motivated
simulaliontecbniqu$ is advantageoussomeactiie researchers.
Fof example,mechanisticmodels
ofp€nicillin fermentarion
hadbeendevelopedby Bajpaiand
workiDson
ReuBI1l. In addition,therewerealsoresearchers
developins software packase t21, hybrid modelling
(t3l.tal,tsl) and dynamicoptimizationt6l.
ISBN:983-2643-15"5
(1)
F-,= 0
The .eactionsinvolvedaresimplifiedasfollow:
5 -r X:.t -+ Pi
(2)
ln this case.the manipulaied variable is the feed raie of S,
which is the subst.ate.
Ovetdv Ma$ Balance
The overall massbalance for ihe fermentation processwas
simplifien and shown in Equation (3) where v representsthe
culture volume, and F is the fe€d rate of subslmle.
(3)
above indicares that a constant densily
made. Becausepenicillin productionis an
38',7
oJ lntenrrli.rol ConJercnceOn ChMi t tnd Biorraees Engnrcariry
Unie^iti Makttlia:;ahah,Kata Kil.bolu
2/r
2qn AuN2AD3
Pneedin{
aerobicfermenirtion process.the lbrmentat'oncuLure rs
continuouslyspargedwith air. The air leavestho fementer
throughthe exhdustgasline lf the a;r enleringthe ferment€r
is dry. water is conlinuallystfippedfrom lhe mednnnand
Ieavesthe systemas vapour.Evaporativewaterlosr can be
significantover a periodoldays [8]. Typically, l0-2oc' of
he r or alor or hc a r o e o \. d u e In e \a P o ra l i odnu n ngone
week of femenration.the actualamountdependingon the
loss.
ofthe iementalion [2]. Hence,evaPorative
lempemrure
betakeninto accoun!in modellingofatermenter.
FL* shoLrld
addition on the loral
ln addilion. the eftbcl of ac;d,4rase
volume changeof the cuhure b.olh. Fdb should also be
includedin Equrlion (3). By includingall theseerms' the
as:
olenll nrassbalanccfo.a ftfmenlercan be expressed
For the Bajpai and Reup model til. distolved oxlgen
concentrationC. and oxygen limitalion constant(ox are
includedin Equation(8) to sivel
,=,,@i;o,.#.c,
(e)
According 10 Birol e, al. t2l, effects of environmental
vadablessuchas pH and lemperatureshouldalso be taken
into account in the specific Srowth expression-These
variablesplay impoftnntroleson lhe qualily and quantilyof
the final product.Consideringthesevadables,lhe specific
growthrateis now given byl
C.
(4)
evapo.ativeloss can be representedby the
The suggested
follo$ing rela!ionships
[2]:
rdt^
Ft,.,= V )G51o
'') \
(5)
Here,f. and I, are the frcezingand boiling enPeratureof
the culture medium lbat were asslmed io have rhe same
propertiesas water, respeclively,and ,l is a sugg€sEd
evapomtionraleof2.5 x 10" l/h al theoperationtempemlure
of 25 'C I2l. Here, the mte of evapomdonapProaches
purposesthe
infinity at theboiling point,andfor engineering
this
to
represent
exponent5 h largeenougb
[2]
Mass Aalance ot Biomass
The equadonfor massbalanceonbiomassis simplifiedas:
v dt
dt
s
r K.+ s)
0)
the maximumspecificgrowth rate,and
H€re,tx represents
Kl is the substfatesatumtionconstant.However the Monod
model is inaccurateto describethe growtb under certa'n
condilion'Ll2l. Ite modeti' only valid lor balancedSrowIh
and should not be applied when grolvlh conditions are
changingrapidtyt8l. Numerousmodificationswe€ madeto
Monod model to improve accuracyof the kinetic model. one
exampleis the Conloiskineticsthal is usedto rcpresentthe
diffusioral limitations thai occur at high biomass
(tlOlitlzl). The Conroiskinetics nodel is
concentrations
givenby equation(8) below.
s
'
''(K,X+Sl
388
Lr +l( 4H l' LH ,K ll{ ^.x+") ,/( .Y+r '
.
.rl
^
lli
1 - i * J :8. llf
' " , J' - 1R/
r'l
ll
,.,,
Ellec. oJpH
Another term to consider in the specific growth rate
expressionis the hyd.ogenion concenttation[H'] l2l The
pH of the culture medium becomes acidic. as lhe
lhe amounlof NH4OH
of biomassincreases.
concentration
in orderto keep
addedinto theculluremediumaho incfeases
rh€pH constantduliDgthe pe.icillin fermentrtion.Basedon
lhis observation,the hyd.ogen ion concentfation is related to
biomassformationas [2]:
d tH' t , .. r x, I a *JIa ,q Jo L ,,,,1r
I n j;
--' A N -
,.// \
-
'l-
",1
(l l)
(6)
whereX is ihe biomassconcent.ationandI is lhe specific
growth rale ofthe biomass.The specificgrowth mtd can be
describedby Monod model (Equation (7)). where fte
growth .ale depetdson the concentmtlo.
microorganisms'
t ]i t9 l ;l l 0 l :[l l l )
o f lim it ingnur . ie n([8
'
-
a is givenas:
+ F")^t
^ [ro*rla't- ta'tiv- c,,"1F
"=--
n+lF;TE,
(t2)
Here, 4 and 16 rcpresent acid and base flow rates in Uh'
C$
in both soLurions,
fespecdvely,wherethe conc€ntration
are assumed€qualto be 3 M. Besidesthat, Birol et al. [2]
aho suggesledrhal undet pH conlrol. (he hydrcSenion
concenlration can be calculated by taking the disassociaion
of water and acid.4)aseinto account as well as the hydrogen
production.The propo.tionalityconstant,7 is estjmatedas
l0' mol [r]/s biomass.
Efect o! TenPqatwe
According to Doran [8], temperaturehd a significant kinetic
effect on reactions. The effe.t of temperatureon the specific
growih rate can be represen!€d by an Anhenius type of
".'(*l'll-".'('#)li
' "'{l-'
( 13)
(8)
ISBN:983-2643-15-5
Pnreedi es ..l t&natiotu
Cdtlurmt
27' -29, trqun2AAl
or Cheni.araM! Biou.Les Ettiwtu1|
Urij,usiti Mdor:h S,bdh K.tu Kiudbdt,
He€, & and A! are lhe constantand dctivationenergyfof
grc*lh. $hile td ,nd td arc the conslantrnd activation
e.er8y ior dealh.respectively.
Mass Daknce on Dissolved Orl|et
Tenpercture Contrcl
!:-
ofthe culturemediumwas keptconstanlar
The tempefatu.e
25 "C. It was conlrolledby a sptit-mngePID controllerlhat
.llors lhe hcating or cooling water flow mte to be
The velociryform ofthe digital PID algorithm
rnanipula|ed.
(asshown;n Equation(14)) was used.
AM y . = A , ( 8,
E" + :::8 .
|,
-!
N
x(cvN-zcvN )+cvN )DMVN
( t4)
Here.Kc is theproporrional
gain,./ is theinte8ralconsran
t, .i
is rhederivariveconstanrand Cyr, -tP, and My! represent
fie cuflent valuesof rhe conrolled variable,set poinl and
conlrolleroutput al lhe cunent saorpleN, respectivety,
with
thecurenr lalueoleftor. ttr (=SPr- Cy,).
Mats Aabnee on Peticillitl
For a fed batch fermeniatjon prccess wilh peniciltin
concentradon.
P and culrurevolume, y. specificpenicillin
productionra!e,tpp, and penicillin hydrolysisconstanr,&
tbemassbalanceequationon penicillinis reducedrc:
dP
dt
..
P dv
V d,
..-
,l st
s
t'"'=t'"p<"+s
K l, . . ) - .
dJ
I
Jl
( t 8)
where / is the specific growrh rate, /pp is the specific
productionrare of penicillin, CL is rhe concenimlon or
dissolved-oxygen
and y is the cuhure yolume. fv, is dre
yield constantwilh unit (g biomass/goxlgen), ypl, is the
yield connant with unir {g penicillin/goxygen),,(/. is the
ove.aUmassrmnsfercoefricienr.The diffe.ence{cL' - C.)
be.ween the maximun possible and aclual oxygen
concenrrur;onsin rhe liqLrid cuhu.e rep.esenls the
conccrrfi .ondr' \ i .g tu.(. for md.. r!.\rer.
The overall massrranste.coefficienrtrh is conslantrn the
original model of Balpai rnd Reup [l]. However,in $is
$ork, K,. is assumedto be a funcrionof agitationpolvei
i npurP "
notr r" reofox)gen /. a..LB ge.reJo) BJ, ey
" nd
a n do ri( t t I . rh i\ i. 5 h o { nin rq i" . o n ii" r rl. , " - " o r
a and I are assignedso rhar the dependence
of penicillin
concentrar;on
on &. marchesctosety!o rbe predicrjonsof
BajpaiandReuptll.
".=".k"\+)'
(19)
Du.ing a fermenhtionprocess,CO, is produced.The CO,
evolutionmle canbe represented
by :
dco. = a)idx
+ atx
dt
c ,"
+ii K),--;;i5
( 16)
where4pisthe maximumspecificpeniciltinproductionrate,
(F is the inhibitionconstant,(iis theinhibirionconstanlfor
productformnrion,(op is the oxygen limitation constanr,
andC.'is thedissolvedoxygenconc€ntmrion.
Mass Balonce on Substrate
-,,,x*l:tsd v
v dt
+ al
(20)
Here, c.r is rhe constant rclaing CO, 10 grcwth, (r: is the
consllnt relatingCO, 10maintenance
energy.and ar is the
constantrelatingCO, ro penjcillinproduction.The vatuesof
o1, c& and sr are cbosenlo give CO, profilessimila. to the
pr€dicLions
oi MonrdgueandLo,trorterslsl. .\ \uggesredb)
B i ml e, dl [2].
Energy Balance
A m.ss b?lanceon substmreis sbownas followl
]:')
Herc, S and X is the subsrrate and biomass concenrration
respectively,fs is rhe yield coefficienr (g biomass/g
substrate),rp is rhe yield coefficieDr (g p€nicillin/g
subslrale),I is the specific growth raie of biomars.tpp 6 me
sp e c if icpr odLc lion
r d ,eo fp e n i c iL n ,l n \ i r rh emc i n l e n anLe
coefficienr.F is the feedflow mte of subst.ate, the feed
$is
substrare
conc€ntration.
and yis the culrurevolumc.
ISBN:983-2643-15-5
. r - r - ! .rp, x - , . x
Mass Balance on Carbo Dioxide (CO,)
The specific penicillin p.oduclionmre, tpp is defined as
( I 6) t ll.
Eq uar ion
*!!=f,x-fix
Massbalanceon dissolvedoxygencar be writrenrs
In fe.menBtion,changesin beah of mixing of subst.ateand
producLswirh rhe brorh are generaly negtig,btesrnce
cell-culturemediaare uruatt) ditule .queoussotu ons wrrh
behaviourcloseto ideal t8l. In addition,tbe effecb of hear
gener ion due ro mechanicatagiration and aemdon power
mput are also assum€dro be negligible €omparedto rhe hear
generaton caused by microbial metabolism. rhe
sunoundings,heatexchanger,
and rateofsensibleenthalpy
gain by lhe flow systemsrream\.Tle energybatancenn a
coi l edrypeheare{ chr' nger.
{ hi chi . sui l abl e
forJ tdbom r oD
scalefermenter has been suSgesledas follow l2ll
189
q
Ptu.zeak|t
Il
' (r.-t) .v p-lrt
"'tu
.l
'.
?+ ., - | --\
.. IJ
t- | \a r l z P
(./0.,,"/d0 is the volumetric heal ptuduction rate. rqr is
assumedrc be coneant and might be rfeatedas a yield
coeffrcienr,and rq, is a constartfor hearproducliondurirg
Thc secondlenn in Equation(22) is impodant
mainlenance.
to lake accountfor the heatptuducliondu.ing malntenance
since melabolicmainlenanceactivitiesgive a siSniiicant
effecton the heatgenerahon.
\2tl
of lbe subsraie.f is lhe ieed
Here, ?l is lhe feedremperature
now raie of the substlale,F. is the flow rate oi the cooling
liquid, p is the density of lhe cullure medium pc rs the
d;nsny of lhe cooling liquid, c,, and .F reprcsentthe heat
capacity of the culture nledium 3nd the cooling liquad
rcspectively.
0.,, is theheatof reaction,a andb areconstants'
Forft;s panicularequation,fte u.il of Fis g/(l-hr)
ProcessSimulation
The modeldevelopedherc was simulatedusingMATLAB
software.The o.dinafy differenlialequalronswere solved
using Fourth-OrderRunge'Kuta algoilhm wjth adapl've
slepsizemechankm.Samplingtime was fixed at 0.02hour
by B i rol eru1.t2l .The w orkofB i rol ,T. / i v'(
assl rggesl ed
slud) and as
as
the
benchmarkfor the simLrlatlon
regarded
aswell asthein;tialvalueswere
such.the kinelicpafamelers
basedon theirwork.Theselre tabulatedin TablesI and2
Reacdonsi. bioprocessesoccur as a result of enzvme
aclivitv and cell metabolismFor heatgeneralioncausedbv
nicrobial reactions/metabolism,Birol er dl. t2l has
suggesedthe following eqtratron:
!9 - =, 4Lv* ,, x v
122)
Trbl, I
Kutett. Panntete5 t
Heattransfercoefficienlof
liquid (caUtr."C)
heatins/cooling
Constant;nheatgenerntion
1000
(catg
i.6783
x l0a
(g/l)
Fed subsrareconcenlLalion
FeedEmperature of subslrate(K)
600
298
5i00
Yield constant(g penicillin/goxysen)
o.20
Anheniusconstantfor cell death
l03l
Yield constant(s penicillin/gglucose)
0.90
Anheniusconslanlfor growth
7xl0r
(s biomass/g
oxysen)
Yieldconslanr
0.04
t ')
s tec o n s ta n(h
P enic r l l 'hny d ro l y s ira
0.04
t0 r0
Yield constant(s biomass/gglucose)
0.45
Constantin Kh
10
ConslBot(moYl)
7x l 0I
Constantr€latingCO, to growlh (mnol
CO,/g biomss)
0.141
Inhibilionconstantfor Produci
formation(g/l)
0.10
ConslantrelalingCO, to maintenance
enersy (rnnol CO,/g bionass.h)
Oxygenlimitationconstml
(with limitat'on)
5x105
ConstantrelatingCOr lo penicill;n
production{mmol COl /l.h)
104
Oxygenlimitationconslant
(with limitation)
2 x lo-'?
Constanr
in Kb
0.4
Inhibitionconstant(g/h)
0.0002
Saturationconstant(g/l)
0.15
Maximum specific growth late (h-')
0.092
Maintenance coefficient on oxygen
(h')
o.467
Specificrateofpenicillinproduclion(hr)
0.005
on substrate
Maintenancecoefficient
0.014
Constantin F|d, ft r)
2.5x10'
0.60
rt
Acdvation energy for cell dealh
50000
Tl
Aclivationenergyfor groath lc!l/mol)
(mon)
Constant
K,
Vdnbles [2]
Time, t (h)
Time, t (h)
K
o.fht.nrati.nol ConJercnceAn Ch.,tical a Bialta.z$ bt?LLeitlg
21
2Er Awrn2003. Unit^iti i\|aldrsidSabah,Kota Kinabalu
v
I
(mol
Proportionality constanl
t 0l
105
trrl/g biomast
or)
390
Constant
3
Densityofmedium (g/l) x Heatcapacity
of medium (caug."C)
1/1500
Yield of heatgeneralion
(caygbiomass)
60
Densilyofcooling liquid (g/l) x H€it
capacityof €oolingliquid (cavg."C)
l/2000
ISBN:98.1-2641-t5-5
PnreIlinq:
nJ hturatianal ConfeEn . On Atenicol a l Sialocc$ ErSnEerntg
UniwBiti MaLaJsiaSabah K.to KL&hdtu
2q^ A4!!2ID3.
21
Tabte2 - Initial Conditions[2)
Tim€, t (h)
(= CL
concentration
oxygen
Dissolved
saruratior)(g/l)
CL
Coz Ca$on dioxideconcenradon(mmol/l)
(mon)
ionconcent.ation
Hydrosen
(s/l)
PenicillincoDcentration
E
0.5
a
5
l0r I
0
0
4",,
s
l .l 6
concenlmtion(91)
Substrare
t5
Fisare 2
PrafLe oJbianast cohc.ntrdttun
Fieure 3
Prclile of pehicillin concentdtion
297
T
Cultufe!olume (l)
100
Biomlssconcentmlion(g/1)
0.1
The sludywasdividedinlo lwo partsl
1 dynamicsimulationof batcbculture
2. closed-loop ope.ation of fed'batch iementalion
Here. pH and lemperaturewere cottrolled using
Results and DiscussioD
The profilesof the outpulvariablesunderDominaloperating
conditions for batch ferrenlation process are shown rn
Figurc I to Figurc 8. The production of Peoicillin started
Accordingto Doran [8], cellsusethe
only rfter a lag-phase.
to
their
new environmert Following the
iag phaseto adapt
phase.After
lag period,the growth enered the acceleration
the substratein the culture medium depleted,cell growth
slowed down, showing a decreasingtrend as shown rn
Figur€ 2. The penicillin concentration started lo increaseat
this stagedue the increas€amountofpenicillin (seeFigure
3).This indicates tha! rhe prccess was in the producl
Fisurc a
Prolile ofdL\oLrcd oryBencon.?ntrutioi
E
s
E
FiBure 5 - Ptofi le of tenpe nt"re
Fisure I - ProJileofsabstrate
ISBNr983-2643-15-5
391
9
Pn(edrrys
aI Intfltarionat ConIe?n.e An Chenicol and Bio ads:Ensineetins
27'
?q' AqN2003, Uniteari Mdhy:ia Sabah Kota Kinabah
6a
Fisue 6 PrcrtleofpH
concettrdtionat initial substate
Fi8urc9 - Substrate
of |0, 15 1nd 25 9t'l
cancentrations
E"
a"
o\ffi.;;-E
d
Fi7ure 7 - Prafile ulcatu"n dioxi.lecohcentr'!ion
FiBurc t0 - Penicillin Concentration at inititll subsrrate
concennatkhr oJ 10, I 5 dnd 25 8,4
F€d-batch Fermentation
Fisure 8 - Pro.JileoI NLture
'otune
oxyget was
dissolved
fermenlation
lhe
During
P.ocess,
lrilised for cellrespiration(seeFigure4) andcarbondioxide
ofgassesin the
was released
by theceUs.Theconcentrations
problem
slatement.
on
good
indicators
systenraho seLveas
It can also be observedthal tempemtureand pH were
reducedwith time (seeFigure 5 md 6). Tbis nav directiv
affect the quality of the prccess. A control svsr€m rs
therefore required to maintain thesevalues
Fed'balch fermentation was accomplished by contin'rousv
feeding the substrate to promoie rhe biosvnthesis of lhe
product- Here, a threshold value of 0.5 8/l was assignerlto
the subslmte concentration. Substm|e fe€ding was acxvated
oncethe strbslrateconcentrationreachedthis threshold value
However, high concentration of substrate mav inhibit the
ceu growth. Hence, controlled supPly of carbon source
(slucose)waspracticedin this study.
6'"
The simulationrsults for differentvaluesof initial substrate
areillustmtedinFigure9 andFigure l0 Here.
concenLadon
it can be seenahatthe penicillin production increaseswrth an
andthenlevels
increasein tbeinitial substrateconcentmtion,
off due to substmtelimitadon in batch fermentation
Fiswe ll - ProJileoJsubstrute
concentation
392
ISBN:983-2643-15'5
Ptd..edinsx oJ ktenational AnJerence On Cheni.al ond Bnrpbes E\ineerhg
27r' 2E Au.ui 2AaJ. urit{rni Mdrysiosobah, Kota Kinabolu
E
a
%-- 6--
Fryrrt t2
i6-
-
-
"m
Prvlile oJbrcnttr concentdtiun
5
FiBute t6
ProfLe of pH
g,
8
":t
"l
FiSure 13 - PrafiLe of peaicillin conceniation
Fisute 14 - Prolile of dissohiedoDsen concentrction
Figurc 17 - Prolle ol carbon .Iioride corce\tatian
Fisurc 18- Profle ol'otume
E*.
FiEurc l5
Profle of tenperuture
ISBN:983-2643-15-5
Fisure 19 ProfileoJsubstatefeednte
393
I
t1,4nat ar ntc r 4l c ..nr A1\L.atal ar t
Pn,c c J :.et.t
2/'
ln rhis wo.k, the substralefbed rale. pH, and temperatufe
sere conrrolledusing PID conrolleE The profiles of the
outpul vadablesunder nominalopemtingcondition where
constdi glucose feed are used duritg the fed-batch
opemtion.areillustratedin Figure ll lo Figure 19.Noletbat
both biomass and penicillin concentmtionshad been
improvedby adding a slow glucoselbed into the batch
fermenter.The controlledsupply of gl coseenabledbolb
giowrh and penicillin production ro lake place
simultaneously
Ii].
By includingPID contolle.s in ftesystem,fte valuesofPH
and temperalure
were ma;nlainedclose!o their desiredset
poinrs. Comparedio the results withoul controllers,rbe
variaiionsfrom the set-pointvalueshad beenreducedAs I
result,the overall perfonnanceof lbe fe.mentationProcess
wasimproved.Thhprovedthe importaiceofcontmlsystenr
Conclusion
An unstructurcdmodel for a fed'barch Penic;llin G
fe.mentatiooprocesshad beendevelo!€din this sludy Tbis
modelincludesadditionalinpul va.iableslike
mathematical
aemirot rate,
feed flow rale of substmte.pH, temperature.
agitalionpower as well as oxtput lariables such as CO,
evolution and heat generation terms. The model was
simulatedin MATLAB environmenland analysesof lhe
dynamicbehaviou.offie processwerecarriedour.F.om fte
observation, a good agreement was shown bellveen the
r$ultsobtaired in this studyand lbe literalure
l2l
Relerences
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[3]
Acknowledgements
The aurhorswish to thank Prol Ali Cinar and Dr Cenk
Undeyfor rheirrechnicalsupporton rhis work This prcject
is fundedby the Ministry of Science,Te.hnologyand the
Envircnmentalrd UniveN;d Teknoiogi Malaysia through
granr.
UTM'PrP Schola$hjpsand IRPA research
2q
R ,t
2643-15-5
ISBN:98.1