Kuliah 1 (Biochemical_Engineering )

8/17/2019 Kuliah 1 (Biochemical_Engineering )

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Biochemical Engineering

Dr. Amyl Ghanem

Department of Chemical Engineering

Dalhousie University


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Outline

• What is biochemical engineering?

• The catalysts

•Relationship to engineering• Historical perspective: penicillin

• The industry: facts

• The industry:• Food, beer and wine• ndustrial chemicals

• !harmaceuticals


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Some definitions….

• "iotechnology: use or development of methods of direct geneticmanipulation for a socially desirable goal# $ometimes a broaderdefinition is used, where biotechnology is applied iology #

• "iomedical %ngineering: engineering on systems to improve human

health

• "ioengineering, biological engineering: wor& on medical oragricultural systems, draws on electrical, mechanical, industrial andchemical engineers#

• Biochemical Engineering! e"tension of chemical engineering principles to systems using a iocatalyst to ring aout desiredchemical transformation#


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#he story of penicillin

'le(ander Fleming)s photo of the dish withbacteria and !enicillin mold, *+-


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#he story of penicillin

*+- *+./0s

1iscovered by 'le(ander Fleming

2hemical synthesisproved to be too difficult

Fermentationroute was chosen

%fforts to increase production•cell line selection•medium optimi3ation

•process development

Full scale production

15+ years


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Biocatalyst! cells and en$ymes

*/4/ µm *45 µm


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%n3yme: 'cetylcholinesterasesi3e range in nm

E + S E-S E + P


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#ypical chemical processing

'

"

'6" !

! '"

temperatureflowrate

'

!

"

Reactor $eparation


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Cell as a ioreactor

!roduct :

cellssmall moleculeen3yme '

!21 etc#

?

Reactor inside a reactor $eparation

reactor

'

!

cell

"21

% !

'


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Bioprocesses are %special&…….

• 2ells are living organisms that re7uire specific conditionsfor growth, production

• 2ells grow in culture medium 8nutrients9 that may

support other cell types 8contamination9• "ioproducts are often sensitive to e(ternal conditions 8T,

pH9 and can easily be destroyed 8separations9

• !roduct is generally very dilute in bioreactor medium

• any byproducts in medium to remove


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….ut they have their advantages'

• 2ells will often perform reactions that are too difficult todo synthetically 8penicillin9

• 2ells can turn basic nutrients 8for e(ample, agricultural

waste9 into valuable products• 'ma3ing diversity of products from cells

• 2ells can be modified to increase product diversity evenmore;

• %n3ymes are highly specific catalysts with high catalyticpower


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IndustryB.Sc. M.S. Ph.D.

/// *++* /// *++* /// *++*

2hemical #= .#* >-#* -#. .<

Fuels *#< *# -#5 *

%lectronics *5#< #. #- ># *+ .#-Food2onsumer !roducts **#. =# .#5 .#5 #- 5#<

aterials >#> #= =#* 5#- ># /#+ /#-

%ngineering $ervices +#- -# */#= *.#+

"usiness $ervices and

@therA

**#


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)ndustry in Canada! Biotechnology

• >5- "iotech companies in 2anada in *+++

• B*#+ billion in revenue

• =


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)ndustry in Canada! Bioproducts

Firms that produce fuels, chemicals, materials andspecialty products using biological feedstoc&s andbioprocessese". alcohol from agricultural and forest feedstoc*+ en$yme

production companies

•=54*// companies that underta&e RD1 andmanufacturing

•B*//4*5/ million in sales each year •*5//4/// people employed•Eery young industry;;


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)ndustry in Canada! ,edical Devices

• -// manufacturing firms in /// 8+/C2anadian4owned9

• >#* billion in revenue, *#< billion of which

were e(ports• *-,/// people employed

• e(9 cardiovascular devices and treatments

such as heart valves and %2 systems• in vitro diagnosticsG imagingG dental

implants and materials


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)ndustry in Canada! Chemicals

• n ///, there were *,// establishmentsoperating in 2anada#

• They employed appro(imately =,5//employees#

• 2anadian shipments in /// were valuedat B>/# billion


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)ndustry -ocus! -ood and everage


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)ndustry -ocus! -ood and everage

Fermentation !roducts

• cheese

• soy products• yoghourt• wine, beer • bread

%n3ymes

• adust food flavour

• adust food te(ture• improve nutritional

7uality

• high fructose cornsyrup


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-ermentation

• ' form of anaerobic respiration occurring in certainmicroorganisms 8e(# yeasts9

• 'lcoholic fermentation is a series of biochemicalreactions by which pyruvate is converted to ethanol and

2@,#


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Metabolic pathways in e.coli


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C / 01 O 2 1 C 1 / 3 O/ 4 1 CO1

• 2ommon yeast saccharomyces cerevisae used in ma&ing wine,

beer, bread by above reaction#• 1ifferent strains of yeast can tolerate different alcohol

concentrations#• Theoretically, *-/ g of sugar will produce + g of ethanol

'ctual yield is only -.#< g of ethanol

∀ ρ%t@H 8/°29 I /#=-+ gmJ

• volume of ethanol I -.#< g ( mJ I */=# mJ /#=-+ g

• volume of the alcohol and water contracts by /#=C so*/=# mJ ( *#//= I */- mJ for an overall alcohol

concentration of */#-C 8vv:*/-*///9#


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• "ri( 8"/9 is a density measurement that indicates thepercentage of sugar in *// g of a sugar4water solution#"ri( can be calculated by:

• "ri( I Kg sugar8g sugar 6 g water9L ( *//

• "ri( units can be used to predict the alcohol content inwine#

• C potential alcohol 8vv9 I /#5= ( "ri(initial


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Beer ma*ing

• alting: grains 8barley, rice9 are steeped in water untilgermination and then dried before a plant develops# The starches inthe grains get converted to sugars by en3ymes#

• "rewing: finely ground malt is turned into a sweetened li7uidby adding warm water added and heating to around =5o where thesugars get dissolved# rain is filtered out, and its boiled forsterili3ation and concentration 8wort9

• Fermentation: the yeast turns the sugar in the wort intoalcohol, a process that ta&es about */ days#


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5ine ma*ing

8*9 Meast !roliferation 4 aerobico(ygen is needed to sterol productionincreased yeast robustness

89 nitial Fermentation 4 anaerobicsugar is converted to alcoholduration times typically 5 4 * days

8>9 $econdary Fermentation 4 malolacticlactic bacteria metaboli3e malic acid to lactic acidlowered acidity and wine NsofteningO occursvery typical for red wines


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6rocess flo7sheet for 7ine


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-actors affecting yeast fermentation

• Meast $pecies

• Temperature

• $ugar concentration• pH

• Eitamins

• $ulfur dio(ide 8$@,9


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)ndustry -ocus! #e"tiles


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Stone 7ashing denim

1enim is faded byabrasive action ofpumice stones

ndigo dye adheresto denim surface

2ellulase en3ymeremoves some of the dyeby partially hydroly3ing thecotton surface

•new loo&s•lower costs•shorter treatment times•less solid waste

•wea&ens the fabric

traditional

method ne7 method


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Detergents

• 1etergent industry is the largest single mar&et for en3ymesat 5 4 >/C of total sales

• 1irt comes in many forms and includes proteins, starchesand lipids 8fats and oils9

• proteases, amylases, lipases are en3ymes used indetergents

• en3ymes allows lower temperatures and less agitation forwashing

Inner core of enzyme plus

preservative bound ith !"!

#rotective a$y coat that

disperses in the ash


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)ndustrial Chemicals

%(amples:

• organic acids produced from Aspergillusniger , citric acid used in soft drin&s

• Pylanase used for wood pulping andbleaching


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Agricultural

%(amples:

• Recombinant bovine somatotropin 8b$T9for increasing mil& production

• "io4insecticides for crop protection

• !hyto4vanilla8tm9 flavor derived from

tissue culture


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Environment

• 2leanup of ha3ardous waste sites usingbacteria that feed on pollutants

• "acteria used for bio4remediation

• wastewater treatment• "iosensors: use biological activity to

detect to(ic substances

• R$Q Water tests: antibody based &it todetect low level of solvents such asben3ene


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-uel ethanol


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)ndustry -ocus! 6harmaceuticals


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Phase II clinical trialsin 100 to 300 patients

The Drug Development and Approval ProcessThe drug discovery and approval process takes and average of

15 years and costs almost $00 millionsource! Pharmaceutical "esearch and #anufacturers of America %ashington D& 1''(

Discovery ofa promisingcompound

Preclinical testingin animals

Phase III clinical trialsin 1000 to 3000 patients

)DA revie* andapproval

Drug may +e prescri+ed +y physicians

1 year

3 years 1' months

(,5 years - years

Phase I clinical trialsin healthy volunteers


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6roducts

• $mall molecules and metabolites

• antibiotics

• !rotein drugs

• Eaccines• 'ntibodies, onoclonal antibodies 8'b9

%o& Recombinant 1' technology means bacteria andyeast can produce human proteins li&e insulin


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6enicillin fermentation


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1883 5orld mar*et for iopharmaceuticals

%nbrel Rheumatoid arthritisand psoriasis

'mgenWyeth B>,,*5. S$

milRemicade Rheumatoid arthritis

and 2rohn0s diseaseohnsonDohnson2entocor $chering !lough

B ,5>5 S$mil


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%pogen $timulation of red bloodcells for treatment ofanemia associated withchronic renal failure

'mgen B ,.55 S$mil

eulasta $timulation ofproduction of whiteblood cells for protection

against chemotherapycomplications

'mgen B ,-- S$mil

eoRecor mon%pogin

$timulation of red bloodcells

enentechRoche2hugai B *,=*/ S$mil

Herceptin "reast cancer enentechRoche B *,


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,onoclonal antiodies


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9e7 challenges….

ncreasingly, bacteriaand yeast cannotcorrectly form the

human protein:

animal cell culture

e": mouse cellsre;uire even more

careful treatment Large quantities


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Opportunities for you<

The "ioproducts industry Nneeds staff thatbridge the &ey disciplines of biology,

chemistry and engineeringO

2anada0s nnovation $trategy , //*overnment of 2anada"ioproducts $ector !rofile


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,ain )ssues

• Types of reactors to provide high o(ygen transfer

• 'ppropriate cell and medium selection

• $terili3ation and maintaining sterility, no crosscontamination

• n pharma, product purity and 7uality impedes processchange

• 2ells and molecules are sensitive to e(treme conditions

• rowth rate and reaction rates are small

• !roduct is usually very dilute• on traditional methods of separation

• @ften batch operations

Kuliah 1 (Biochemical_Engineering )

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