PlsLory of 8loprocess and
lermenLauon
1he good, Lhe bad, and Lhe smelly
lmporLance of 8loprocess 1echnology
21sL cenLury saw a greaL developmenL ln Lhe eld of geneucs and
molecular blology, whlch has broughL world-wlde lnLeresL ln
bloLechnology.
1he ablllLy Lo manlpulaLe unA has radlcally changed our percepuons of
medlclne, agrlculLure and envlronmenLal managemenL.
Coupled wlLh sclenuc breakLhroughs ln gene expresslon, proLeln
englneerlng and cell fuslon has ln Lransformlng bloLechnology lndusLry Lo
dellver revoluuonary new producLs and servlces.
1he ulumaLe goal of bloLechnology ls Lo use knowledge of molecular
blology and cell manlpulauon for Lhe large scale processlng of blologlcal
maLerlal.
!"#$ &'() #$ *+),))-. /0 1(#2#3& /#'4-5"3')'&0 6#4" /#'12'5-$$
.-7-)'18-349
8loprocess developmenL has been an essenual parL of many foods,
chemlcal and pharmaceuucal lndusLrles.
8loprocess operauon make use of mlcroblal, anlmal and planL cells and
componenLs of cells such as enzymes Lo manufacLure new producLs and
desLroy harmful wasLes.
use of mlcroorganlsms Lo Lransfer blologlcal maLerlal for producuon of
fermenLed foods has lLs orlglns ln anuqulLy.
Slnce Lhen, bloprocesses have been developed for an enormous range of
commerclal producLs, from relauvely cheap maLerlals such as lndusLrlal
alcohol and organlc solvenLs Lo expenslve speclalLy chemlcals such as
anubloucs, Lherapeuuc proLelns and vacclnes.
Cur ablllLy Lo harness Lhe capablllues of cells and enzymes has been
closely relaLed Lo advancemenLs ln mlcroblology, blochemlsLry and cell
physlology.
As our knowledge ln Lhese areas ls expandlng rapldly, Lools of modern
bloLechnology such as recomblnanL unA, gene probes, cell fuslon and
ussue culLure oer ways Lo produce new producLs or lmprove blo
processlng meLhods.
Modern 8loLechnology has allowed us Lo envlslon sophlsucaLed
medlclnes, culLured human ussues and organs, blochlps for new-age
compuLers, envlronmenLally-compauble pesucldes and powerful
polluuon-degradlng mlcrobes.
So, blology ls playlng a key role ln revoluuon of lndusLry. 8uL Lhe maln
problem ls brlnglng Lhese new producLs concelved and parually developed
ln Lhe laboraLory Lo Lhe lndusLry, so LhaL all can en[oy Lhe frulL of modern
bloLechnology.
1hls requlres exLenslve knowledge of englneerlng skllls. 1hus bloprocess
englneerlng ls Lhe fuslon of blologlcal knowledge and englneerlng skllls.
:#$4'20 '* ;#'12'5-$$
8loLechnologlcal processes have been essenual for human survlval and for
sausfylng varlous needs LhroughouL human culLure.
Modern blo-process Lechnology ls an exLenslon of anclenL Lechnlques for
developlng useful producLs by Laklng advanLage of naLural blologlcal
acuvlues.
Larly bloLechnologlcal processes LhaL use mlcroorganlsms Lo produce a
cerLaln producL have been used for several Lhousand years.
When our early ancesLors made alcohollc beverages, Lhey used a
bloprocess: Lhe comblnauon of yeasL cells and nuLrlenLs (cereal gralns)
formed a fermenLauon sysLem ln whlch Lhe organlsms consumed Lhe
nuLrlenLs for Lhelr own growLh and produced by-producLs (alcohol and
carbon dloxlde gas) LhaL helped Lo make Lhe beverage.
AlLhough more sophlsucaLed, Loday's bloprocess Lechnology ls based on
Lhe same prlnclple: comblnlng llvlng mauer (whole organlsms or enzymes)
wlLh nuLrlenLs under Lhe condluons necessary Lo make Lhe deslred end
producL.
1he Lgypuans brewed beer and baked producL ln Lhe <4" 8#))-33#+8 ;=9
A baslc purlcauon sLep, Lhe dlsullauon of eLhanol, was applled ln Lhe >3.
8#))-33#+8 ;= ln Lhe chlna.
Modern bloLechnology was sLarLed ln Lhe ?@4" 5-34+20 when general
knowledge abouL blologlcal sysLem, Lhelr componenLs, and lnLeracuon
beLween Lhem grew.
ln Lhe rsL half of Lhe >A4" 5-34+20 Lhe rsL large scale fermenLauon
processes, namely clLrlc acld and penlclllln, were reallzed.
1he process of recomblnanL gene Lechnology Lhen led Lo a subsLanual
lncrease ln Lhe number of bloprocesses and Lhelr producuon volume
sLarung wlLh lnsulln, Lhe rsL producL manufacLured wlLh recomblnanL
Lechnology, ln Lhe -(2)0 ?@BA$.
1he developmenL of geneuc englneerlng and monoclonal anubody
Lechnology, whlch sLarLed ln Lhe ?@CA$, has led Lo Lhe lnLroducuon of a
large number of new producLs wlLh appllcauon ln many dlerenL areas.
1he mosL hlghly vlslble appllcauons have been ln Lhe area of human healLh
care, wlLh producL such as human lnsulln, lnLerferons, ussue plasmlnogen
acuvaLor, eryLhropoleun, colony-sumulaung facLors, and monoclonal
anubody-based producLs.
ln addluon slgnlcanL new producLs for agrlculLure, food lndusLry, ne
chemlcals and Lhe envlronmenLs are also under lnLense developmenL.
1hus Lhe eld of blo processlng has become a very lmporLanL parL of
bloLechnology.
1oday, Lhe blo-lndusLrles have reached a crlucal slze and are addluonally
based on a broad undersLandlng of genomlcs, proLeomlcs, blolnformaucs,
geneuc Lransformauon and molecular breedlng.
1he presenL worldwlde sales of bloprocess producLs are reporLed Lo
range beLween 13 and 60 bllllon dollar, dependlng upon Lhe source.
PlsLory of lermenLauon
Age old appllcauons:
1. Wlne/ 8eer/ SplrlLs
2. Cheese and ?oghurL
Louls asLeur:
PypoLheslsed LhaL bacLerla spolls wlne
SuggesLed LhaL wlne be heaLed Lo klll
bacLerla
Pence: pasLeurlzauon of mllk
lermenLauons
ros and Cons
LxLended shelf llfe of food
(ex. Cheese)
Lases ulgesuon (ex. Wlld
rlce)
new [beuer] avours (ex.
ChocolaLe)
Can be unpredlcLable (l.e.
bad bacLerla wln Lhe baule)
new [worse] avours (ex.
Mouldy bread LasLes
Lerrlble)
1he rocess
Aeroblc resplrauon
release of energy from
glucose or anoLher organlc
subsLraLe ln Lhe presence of
Cxygen
CC2, P2C, an energy
produced
Anaeroblc resplrauon
release of energy from
glucose or anoLher organlc
subsLraLe ln Lhe absence of
Cxygen
roducLs: CC2, energy, and
alcohol or varlous organlc
aclds
lermenLauon !"#$%&'$:
Anaeroblc resplrauon of food by
mlcro organlsms
1ypes of fermenLauon:
1. 8acLerlal fermenLauon
2. ?easL fermenLauon
3. Mold and Lnzyme fermenLauon
1. 8acLerlal lermenLauon (4 Lypes)
a) Lacuc Acld 8acLerla
(plckles, sauerkrauL)
b) Aceuc Acld 8acLerla
(vlnegar)
c) Carbon uloxlde 8acLerla
(Ldam, Couda, Swlss)
d) roLeolyuc 8acLerla (cocoa,
chocolaLe)
()*+",%)
2. ?easL lermenLauon
Clu! LLhyl alcohol + CC2
8esL LemperaLure: 27
degree C (warm)
CLher sugars wlll fermenL
(mal, suc, fru)
1oo much salL rulns Lhe
process
When baklng: follow Lhe
reclpe
3. Mold and Lnzyme lermenLauon
Lnzymes ln Mold can be useful:
-8reak down cellulose Lhus gralns easler Lo
chew
-Add avour and LexLure Lo cheeses (ex-
blue)
Wlne
uaLes back Lo Mlddle easL
3000 bc
lermenLauon of grapes
Sclenuc process yeL so
many varlables
Crowlng years aecL
vlnLages
Coee
Coee beans fermenLed by
bacLerla and enzymes (2
meLhods):
1. WeL MeLhod: soaked for
12-24 hours and drled
2. ury MeLhod: washed Lhen
drled for 2-3 weeks
1ea
3000 Au (aL Lhe laLesL)-
CuluvaLed ln Chlna
8olled leaves begln Lo
fermenL
LeLs sLand aL 27 degree C
for 2-3 hrs
1ypes: Creen, Colong, 8lack
ChocolaLe
1.3 mllllon Lons cocoa
produced each year
Supply: W. Afrlca
roduced: S. Amerlca
Lnzyme fermenLauon ln Lhe
sun vla proLeolyuc bacLerla
8luer beans become
sweeLer and brown
lermenLauon around Lhe world
lood, drlnk, sauces,
eL ceLera
Time Fermentation Product Place
Antiquity Bread, vinegar, soy sauce, wine,
beer
7000 B.C. Beer and wine Assyria, Caucasia,
Mesopotamia,
Sumer
6000 B.C Winemaking Georgia
5000 B.C Wine jars Zagros Mountains,Iran
Fermented beverages Babylon
3000 B.C. Beer and fermented milk products Babylon
2600 B.C Bread Egypt
1000 B.C Soy sauce and miso China
600 B.C. Cheese Asia
500 B.C. Preservation of fish and meat
100 B.C. Bread Ancient Rome
Time Fermentation Product Place
1700s Vinegar- from fruit pomace, Gallic
acid
1800s Yeast induced fermentation Erxleben, Germany
1850s 1)Bacteria produce lactic acid which
conserves food
2)Pasteurization heat treatment to
prevent unwanted fermentation
3)Yeast+grape juice
!wine beginning
of the science of food fermentation
Louis Pasteur, France
End of 1800s Composting
1900's Asepuc fermenLauon (excluslon of
unwanLed mlcroorganlsms)
Time Fermentation Product Place
Industrial production of acetone,
butanol,
butanodiol substrates for rubber
production
1930 Discovery of biotechnological method
of organic acids production Citric
acid and gluconic acid
1940s Industrial production of organic acids
1950s Industrial pencillin production first
high cost and high tech process. First
large scale production of
pharmaceuticals. Penicillin was the
first antibiotic - a medication against
bacterial infections
!#8- D-28-34(E'3 12'.+54 F)(5-
1950s 60s Steroid formation by fungal spores
1960s Commercial production of amino acids
by fermentation; Production of MSG
(monosodium glutamate, flavour
enhancer)
Japan
1960s 80s Mycotoxins, treatment and reuse of
wastes (animal, plant and domestic)
1970s Microbiologically produced enzymes-
used in grain processing, sugar
production, fruit juice clarification,
detergent additives
1980s Genetic Engineering techniques
insulin production
History and origins of some fermented foods
Food Approximate year
of introduction
Region
Mushrooms
Soy sauce
Wine
Fermented milk
Cheese
Beer
Bread
Fermented Meats
Sourdough bread
Fish sauce
Pickled vegetables
Tea
4000 BC
3000 BC
3000 BC
3000 BC
2000 BC
2000 BC
1500 BC
1500 BC
1000 BC
1000 BC
1000 BC
200 BC
China
China, Korea, Japan
North Africa, Europe
Middle East
Middle East
North Africa, China
Egypt, Europe
Middle East
Europe
Southeast Asia, North Africa
China, Europe
China
G-3-2() '7-27#-6 '* ;#'12'5-$$
8loprocesses have become wldely used ln several elds of commerclal
bloLechnology, such as producuon of enzymes and anubloucs.
As Lechnlques and lnsLrumenLauon are rened, bloprocesses may have
appllcauons ln oLher areas where chemlcal processes are now used.
8ecause bloprocesses use llvlng maLerlal, Lhey oer several advanLages
over convenuonal chemlcal meLhods of producuon:
" 1hey usually requlre lower LemperaLure,
" ressure, and
" pP (Lhe measure of acldlLy)
" 1hey can use renewable resources as raw maLerlals
" CreaLer quanuues can be produced wlLh less energy consumpuon.
ln mosL bloprocesses, enzymes are used Lo caLalyze Lhe blochemlcal reacuons
of whole mlcroorganlsms or Lhelr cellular componenLs.
1he blologlcal caLalysL causes Lhe reacuons Lo occur, buL ls noL changed ln
lLself.
Aer a serles of such reacuons Lhe lnlual raw maLerlals are chemlcally
changed Lo form Lhe deslred end producL.
AlLhough lL sounds qulLe slmple, Lhls procedure presenLs Lwo ma[or
challenges.
llrsL, Lhe condluons under whlch Lhe reacuons occur musL be rlgldly
malnLalned.
1emperaLure, pressure, pP, oxygen conLenL, and ow raLe are only a few of
Lhe varlables LhaL musL be kepL aL very speclc levels.
WlLh Lhe developmenL of auLomaLed and compuLerlzed equlpmenL, lL ls
becomlng much easler Lo accuraLely monlLor reacuon condluons and Lhus
lncrease producuon emclency.
Second, Lhe reacuons resulL ln Lhe formauon of many unwanLed by-
producLs.
1he presence of conLamlnaung wasLe maLerlal oen poses a Lwo-fold
problem:
" Pow Lo recover or separaLe Lhe end producL ln a way LhaL leaves as
llule resldue as posslble ln Lhe caLalyuc sysLem?
" Pow Lo lsolaLe Lhe deslred producL ln pure form?
1he many poLenual uses of bloLechnology are developed Lhrough
laboraLory procedures LhaL generally produce only small amounLs of
useful subsLances.
As advances ln bloprocess Lechnology, parucularly separauon and
purlcauon Lechnlques, are made, commerclal rms wlll be able Lo
economlcally produce Lhese subsLances ln large amounLs, and Lhus make
Lhem avallable for use ln
" Medlcal research,
" lood processlng,
" AgrlculLure,
" harmaceuucal developmenL,
" WasLe managemenL, and
" numerous oLher elds of sclence and lndusLry.
D+4+2- 1-2$1-5E7-$ '* /#'12'5-$$ 4-5"3')'&0
1he lasL decade we saw an enormous sumulauon from blologlcal sclences
comblned wlLh lnformaucs, e.g. Lhe genomlc sequence of man, planLs and
mlcroorganlsms or Lhe lsolauon of human sLem cells.
Powever, Lhls knowledge walLs Lo be Lransfer Lo Lechnology and markeL producLs.
1he knowl edge of mol ecul ar breedl ng, sLem cel l Lechnol ogy and
pharmacogenomlcs mlghL lead Lo sLrongly personallzed Lheraples and
Lherapeuucs.
lL can expecLed LhaL blocaLalysL such as lnsecL and planL cell and Lransgenlc planLs
and anlmals sooner or laLer wlll reach much broader appllcablllLy, alLhough Lhls
mlghL noL happen ln nexL decade.
1he lncreased use of exLremophlles and Lhelr enzymes and blocaLalysL ln non-
aqueous soluuon wlll broaden Lhe Lechnology plauorm for bloprocesses.
AparL from Lhe recomblnanL Lechnology, Lhe naLurally occurrlng organlsm also
provldes Lhe huge reservolr of new producLs.
8loprocesses wlll be used ln Lhe lndusLrles where Lhey are noL used Loday or
where only lab scale processes are developed.
lL ls expecLed LhaL Lhe comblnauon of bloLechnology, nanoLechnology and
lnformauon Lechnology wlll lead Lo subsLanual raLe of progress and expanslon.
1he use of lnformauon Lechnology has already led Lo lmprovemenL ln Lhe
screenlng and developmenL of new drugs and ln Lhe undersLandlng of
blologlcal sysLem.
lL mlghL also lead Lo blo-chlps for compuLers LhaL replace slllcon based chlps.
1he blo-lndusLrles are sull lmmaLure and producuons are relauvely low.
1herefore noL only do Lhe sLraln and fermenLauon have Lo be opumlzed and
producuon scales lncreased, buL also a subsLanual progress ln downsLream
Lechnologles ls necessary.
Modelllng, slmulauon and accompanylng susLalnablllLy assessmenL wlll
play a cruclal role ln achlevlng a full explolLauon of Lhe poLenual of blo
processlng.
Powever, ln some areas ln Lhe expecLed posluve developmenL wlll reach
lLs full poLenual only lf Lhe publlc accepLance of bloLechnology can be
lmproved conslderably.
1he expendlng developmenL of blofuels ls an lmporLanL example.
Pere, an open and consLrucuve dlalogue based on Lhe sound susLalnablllLy
ls cruclal, and sclenusL can make a valuable conLrlbuuon Lo Lhls dlscusslon.
lurLhermore well Lralned blo-englneers are essenual for Lhe exlsung
poLenual of bloLechnology Lo be reallzed.
H')- '* ;#'12'5-$$ I3--2
8esponslble Lo plan and conducL lndependenL work requlrlng [udgmenL ln
Lhe evaluauon, selecuon, appllcauon and adapLauon of englneerlng
Lechnlques, procedures and crlLerla.
uevlse new approaches Lo problems, and prepare or modlfy drawlngs,
speclcauons, calculauons, charLs and graphs, and monlLor work for
compllance Lo appllcable codes, accepLed englneerlng pracuces.
!01#5() .+E-$:
ConcepLual englneerlng and deslgn.
ueLalled englneerlng and deslgn.
rocess developmenL reporLs.
8lock llow ulagrams (8lu) and rocess llow ulagrams (lu).
rocess and lnsLrumenLauon ulagrams (&lu).
rocess englneerlng calculauons.
Mass/LnLhalpy balance.
8asls of deslgn process scope documenLs.
rocess equlpmenL speclcauons, process analysls and daLa sheeLs.
user 8equlremenL Speclcauons (u8S).
ro[ecL sLaLus reporLs.
LqulpmenL llsLs, llne llsLs, and valve llsLs and equlpmenL analysls
rocess equlpmenL consLrucuon speclcauons.
I$$-3E() D+35E'3$
AccounLable for Lhe successful compleuon of asslgned englneerlng Lasks
and preparauon of englneerlng dellverables.
lnLerface wlLh oLher lnLernal englneerlng dlsclpllnes (mechanlcal, clvll/
sLrucLural, elecLrlcal, lnsLrumenLauon, auLomauon, archlLecLure, eLc.) Lo
ensure a coordlnaLed deslgn and compleLe englneerlng dellverables.
aruclpauon ln CllenL/conLracLor meeungs, resolvlng Lechnlcal lssues,
preparauon of meeung mlnuLes and acuon lLems llsLs.
lleld Lrlps Lo CllenL slLe as requlred Lo deLermlne exlsung as-bullL
condluons.
Slze and selecL equlpmenL, maLerlals, and process sysLems.
AsslsL ln Lhe preparauon of englneerlng pro[ecL proposals.
Check vendor drawlngs Lo lnsure deslgn accuracy and compllance wlLh
speclcauons.
uevelop process and pro[ecL requlremenLs.
CoordlnaLe and check englneerlng dellverables.
ConsLrucuon supporL acuvlues lncludlng respondlng Lo submluals.
erform process slmulauons/calculauons.
MonlLor/supervlse less experlenced 8loprocess Lnglneers.
Auend meeungs wlLh CllenLs Lo dlscuss deslgn deLalls.
uevelop sLandard sysLem deslgns.
J-$#&3 IK1-2#-35-
8loreacLors (lermenLauon/Cell CulLure).
roducL 8ecovery (CenLrlfugauon, Cell ulsrupuon, Cryopreservauon).
urlcauon (ChromaLography, ul/Cl/1ll/Lyophlllzauon).
8lowasLe ueacuvauon/neuLrallzauon.
8ulk Solld SLorage and uellvery.
8ulk Llquld SLorage and uellvery (Causuc, Acld, volaule SolvenLs).
rocess uullues (Chllled Clycol/WaLer, lanL SLeam, Compressed Alr, CuA,
PoL/Cold
PeaL 1ransfer Medla and SysLems
Clean SLeam.
PoL/Cold WaLer for ln[ecuon (Wll).
8everse Csmosls (8C)/ul harmaceuucal WaLer SysLems.
Cas SLorage and uellvery (Cxygen, Pydrogen, nlLrogen, Pellum, Argon,
CC2, vacuum).
SanlLary lplng ueslgn.
Clean-ln-lace SysLems (Cl),
SLeam-ln-lace SysLems (Sl).
LM#)) (3. $1-5#() 2-N+#2-8-34$O )#5-3$#3&
knowledge of AuLoCAu a plus.
8A1C SafeLy 1ralnlng.
Llcensed L or Ll1 ls preferred.
LxcellenL compuLer skllls ln Mlcroso SulLe.
lamlllarlLy wlLh Al, ASML, AnSl and lSA sLandards a plus.
re-employmenL drug and alcohol screenlng.
8ackground screenlng lncludlng prevlous employmenL, educauon, crlmlnal
hlsLory, and drlvlng record verlcauon
knowledge of regulaLory guldellnes, lncludlng luA and cCM.
knowledge of hazardous area requlremenLs and cerucauons relaLed Lo
lnsLrumenL lnsLallauon.
Lxperlence wlLh faclllLy deslgn and consLrucuon.
Lxperlence ln worklng wlLh muluple dlsclpllne englneerlng pro[ecLs.
Successful experlence lnLerfaclng wlLh CllenLs.
SLrong communlcauon skllls, lncludlng wrlung skllls ln preparlng reporLs,
analyses, eLc.
;#'2-(54'2
8loprocess ow charL
Penicillin production
G)+4(8(4- 12'.+5E'3 PQLGR ST#3'8'4'U
I4"(3') F2'.+5E'3
V(5E5 (5#. 12'.+5E'3
W1$42-(8 12'5-$$#3& #3 /#'12'5-$$
J'63 $42-(8 12'5-$$#3& #3 /#'2-(54'2
