dsp of some prdts vii sem

8/11/2019 Dsp of Some Prdts VII Sem

1/76


2/76

2


3/76


4/76

Fermentation for Citric Acid Production

For a long time the production of citric acid has been based on the use of molasses

and various strains ofAspergillus nigerand occasionallyAsp. wenti.

Production by Penicilliumis available, in practice are not used because of low

productivity.

Recently yeasts, especially Candida spp.(including Candida quillermondi) have

been used to produce the acid from sugar.

Japanese workers described a method to produce the acid by paraffins by bacteria

and yeasts. Among the bacteria wereArthrobacter paraffineusand corynebacteria;

the yeasts include Candida lipolyticaand Candida oleiphila.

Fermentation with molasses and other sugar sources can be either surface or

submerged. Fermentation with paraffins however is submerged.

(a)Surface fermentation: Surface fermentation using Aspergillus niger may be doneon rice bran as is the case in Japan, or in liquid solution in flat aluminium or

stainless steel pans.

Special strains ofAsp. niger which can produce citric acid despite the high content

of trace metals in rice bran are used. The citric acid is extracted from the bran by

leaching and is then precipitated from the resulting solution as calcium citrate.


5/76

Fermentation for Citric Acid Production

(b)Submerged fermentation:As in all other processes where citric acid is made

the fermentation the fermentor is made of acid-resistant materials such as

stainless steel.

The carbohydrate sources are molasses decationized by ion exchange, sucrose or

glucose. MgSO4, 7H2O and KH2PO4at about 1% and 0.05-2% respectively are

added (in submerged fermentation phosphate restriction is not necessary).

The pH is never allowed higher than 3.5.

Copper is used at up to 500 ppm as an antagonist of the enzyme aconitase which

requires iron.

1-5% of methanol, isopranol or ethanol when added to fermentations containing

unpurified materials increase the yield; the yields are reduced in media with

purified materials. As high aeration is deleterious to citric acid production, mechanical agitation is

not necessary and air may be bubbled through. Anti-form is added.

The fungus occurs as a uniform dispersal of pellets in the medium.

The fermentation lasts for five to fourteen days.


6/76

Extraction

The broth is filtered until clear.

Calcium citrate is precipitated by the addition of magnesium-free Ca(OH)2.

Since magnesium is more soluble than calcium, some acidmay be lost in the solution as magnesium citrate ifmagnesium is added.

Calcium citrate is filtered and the filter cake is treated withsulfuric acid to precipitate the calcium.

The dilute solution containing citric acid is purified bytreatment with activated carbon and passing through iron

exchange beds. The purified dilute acid is evaporated to yield crystals of citric

acid.

Further purification may be required to meet pharmaceuticalstipulations.


7/76

7

The Distillery Flow Diagram: From Corn to Ethanol Plus Co-products

1 bushel

of corn(56 lbs)

Starch

(32 lbs)

Milling

Fermentablesugar

(36 lbs)

Liquefaction

Saccharification

Ethanol

(17.6 lbs)

+DDGS

(17 lbs)

+Heat(7450 BTU)

+

CO2(18.4 lbs)

Fermentation

Recovery

Dryhouse


8/76

8

Fermentation Fundamentals

Key Ingredients

Starch (sugar source)

Enzymes (breakdown of starches) Yeast (conversion of sugar to ethanol)

Key Process Components Enzyme addition

Yeast propagation

Fermentation cycle

EnergyCOOHHCOHC 2556126

22


9/76

9

Process Description Milling Cooking and mixing

Milled corn and cook water a-Amylase to break down long polymer chains (starch), reduce solids

Solubilization of sugars

Release of bound sugars: starch is bound to protein and fiber which is released during

cooking

Gelatinization: absorb water so enzymes can react with molecules

Liquefaction

Using a-Amylase to break down starches to shorter chain molecules

Saccharification and Fermentation

Batch processs (~ 50-60 hours)

Exothermic Glucoamylase is used to break down short chained molecules to glucose

Yeast is added to convert glucose to ethanol


10/76

10

Water Balance

Methanator

Slurry Tank

Process Water

Liquefaction

Backset

Beer Feed

Milling


11/76

11

Fermentation

Slurry TankLiquefaction

Backset

Beer Feed

FermenterYeast Propagation

Enzymes


12/76

12

Distillation

Separate Ethanol from non-fermentable

components

Dehydration

Azeotropic Distillation

Molecular Sieves Non-Fermentables

Centrifugation

Evaporation

Process Description


13/76

13

Distillation

Beer Feed

Evap. Steam

Steam Flow

Sieve BackPressure

Rectifier Reflux Sieve Feed

Vaporizer Temperature


14/76

14

Dryer, Evaporator and TO

Steam Flow

Centrifuge Feed

Whole Stillage

Thin Stillage

Syrup Tank

Wet Cake

Pad

Evaporators

Dryers


15/76

15

Control Strategy

Ethanol Plant-Wide Optimizer

Dryer Evap TOAPC&Distill/Sieve APC

Fermentation APCSlurry/WaterbalanceAPC

Mv setpointsPlant and constraintMeasurements (CV)

Energy,feedstock,ProductValues

$ costs


16/76

Separation:

- The biomass is separated by filtration

- The liquid is transferred to recovery process:

- Separation of citric acid from the liquid: precipitation

calcium hydroxide is added to obtain calcium citratetetrahydrate wash the precipitate dissolve it with

dilute sulfuric acid, yield citric acid and calciumsulfate precipitate bleach and crystallization anhydrous or monohydrate citric acid.

Industrial Production of Citric Acid


17/76

Industrial Production of Ethanol

Application of Ethanol:

- Medical

- Fuel

- Industrial


18/76

Ethanol Production by Anaerobic Bioprocesses

Glycolysis


19/76

- Microorganism: S. cerevisaefor hexose

Candida sp. for lactose or pentoseGenetically modifiedE. coli

- Ethanol production is growth-associated with S. cerevisae.

- Medium requirements for high production- Carbon source: sugar cane, starch materials (e.g. corn, wheat), cellulosic

materials (?!). yield: 0.51 g ethanol/g glucose.- N, P, minerals.- Anaerobic- 100g/L glucose are inhibitory for yeast.- 5% (v/v) of ethanol are inhibitory for yeast.- pH:4-6 for 30-35 oC.



20/76

Bioreactor: batch, continuous or with cell recycle

95% conversion of sugars with a residence time of

40 h in batch reactor21 h in continuous reactor without cell recycle1.6 h in continuous reactor with cell cycle

By-products: glycerol, acetic acid, succinic acid.


Separation:

- Distillation to obtaining 95% (w/w) of ethanol-watermixture, followed by

- Molecular sieves to removing water from the

mixture to get anhydrous ethanol.


21/76

Ethanol Production

http://www.cleantechblog.com/uploaded_images/production_process-718492.jpg


22/76

Purification of Citric AcidA typical method used for purification of citric acid from a

fermentation broth involves two major purification techniques:

precipitation and filtration. The following schematic displays a

generic citric acid purification scheme. The scheme will be

discussed in detail in the next few slides.

ffffPrecReact citric acid

with calcium

carbonate

Filter

precipitateReact precipitate

with sulfuric

acid

Filter

precipitatePurifiedCitric

Acid


23/76


24/76

Purification of Citric AcidThe calcium citrate is then washed, heated, and filtered to remove

any number of the contaminants. Depending on the specific

design of the purification scheme, filters can be placed before the

first reaction with calcium carbonate, in series between the two

precipitation reactions or in any other combination that works.

Also, it is important to choose the best kind of filter for what isbeing removed. For simplicity, the filters here will remove larger

contaminants first (sucrose and salts) and the smaller

contaminants later.

Kirk 15

Calcium Citrate as

a precipitate plus

contaminants

Filter

Ex. Plate filter, Rotary

presses, rack-and-

frame presses

Calcium Citrate,

biomass, water


25/76

Calcium Citrate,

biomass, water

Purification of Citric AcidTo crack the calcium citrate precipitate, sulfuric acid is needed.

The temperature of this reaction should stay below 60C. Thereaction will produce free citric acid and a new precipitate,calcium sulfate, which will need to be removed later. Thestoichiometric coefficients for this reaction are all one.

Kirk, 15

CSTR Calcium sulfate as aprecipitate, free citric

acid, biomass, water

Sulfuric

Acid, SO4


26/76

Purification of Citric AcidIn this filter, the calcium sulfate is washed away from the citric

acid and the leftover biomass is removed. Again, thecontaminants that were present in the fermentation broth can beremoved by additional filtration means, such as microfiltration orultrafiltration.

Kirk 15

Filter

Ex. Plate filter, Rotary

presses, rack-and-

frame presses

Citric acid,

water

Calcium sulfate as a

precipitate, free citric

acid, biomass, water


27/76

Purification of Citric Acid

Further PurificationCitric acid can be produced in two formsmonohydrate andanhydrous. These forms may require additional purification steps

to reach the desired purity.

1. Monohydrate contains one water molecule for every citric acid

molecule

Requires repeated crystallization until water content is approx. 7.5-8.8%

2. Anhydrous Processed to remove all water from end product

Prepare by dehydrating the monohydrate citric acid product at atemperature above 36.6C

Kirk 16,17

KICgroup 1


28/76

Citric AcidLime/Acid

Fermentation Precipitation

Acidification Crystallization

Lime

CalciumCitrate

Sugars Residue

CitricAcid

SulfuricAcid Water

Gypsum


29/76

Purification ConclusionOnce the product has been brought to the desired purity, it would

be sent to packaging and distribution.

In summary, there are many different methods and types ofequipment that make up a purification scheme. Some of the

more common types or purification were discussed in the firsthalf of this tutorial. The second half of the tutorial dealt with aspecific citric acid purification scheme that utilizes precipitationand filtration to recover free citric acid from a contaminatedfermentation broth.

Citric

AcidPurification


30/76

INDUSTRIAL ALCOHOL PRODUCTION


31/76

Ethanol (ethyl alcohol, grain alcohol) is a clear,colorless liquid with a characteristic, agreeable odor.

In dilute aqueous solution, it has a somewhat sweetflavor, but in more concentrated solutions it has aburning taste.

Ethanol, the word, alcohol derives from Arabic al-kuhul, which denotes a fine powder of antimony usedas an eye makeup. Alcohol originally referred to anyfine powder, but medieval alchemists later applied theterm to the refined products of distillation, and thisled to the current usage.


32/76

Uses of Ethanol (i) Use as a chemical feed stock: In the chemical industry, ethanol is an

intermediate in many chemical processes because of its great reactivity as shown

above. It is thus a very important chemical feed stock. (ii) Solvent use: Ethanol is widely used in industry as a solvent for dyes, oils, waxes,

explosives, cosmetics etc.

(iii) General utility: Alcohol is used as a disinfectant in hospitals, for cleaning and

lighting in the home, and in the laboratory second only to water as a solvent.

(iv) Fuel: Ethanol is mixed with petrol or gasoline up to 10% and known as gasohol

and used in automobiles.

D t d Al h l


33/76

Denatured Alcohol

All over the world and even in ancient times, governments have

derived revenue from potable alcohol. For this reason when alcohol is

used in large quantities it is denatured or rendered unpleasant todrink.

The base of denatured alcohol is usually 95% alcohol with 5% water;

for domestic burning or hospital use denatured alcohol is dispended

as methylated spirit, which contains a 10% solution of methanol,pyridine and coloring material.

For industrial purpose methanol is used as the denaturant.

In the United States alcohol may be completely denatured (C.D.A.

completely denatured alcohol) when it cannot be used orally becauseof a foul taste or four smelling additives.

It may be specially denatured (S.D.A.specially denatured alcohol)

when it can still be used for special purposes such as vinegar

manufacture without being suitable for consumption.


34/76


35/76

A bushel of corn weighs 56 pounds and will

produce at least 2.8 gallons of ethanol , 17

pounds of distillers grain & 18 Pounds ofCO

2

In 2005, 97 ethanol plants in 21 states

produced a record 3.904 billion gallons of

ethanol


36/76

Ethanol can be made by a dry millprocess or a

wet millprocess.

Most of the ethanol in the U.S. is made using

the dry mill method. In the dry mill process,

the starch portion of the corn is fermented

into sugar then distilled into alcohol.
http://www.ethanol.org/pdfs/drymilling.pdfhttp://www.ethanol.org/pdfs/wetmilling.pdfhttp://www.ethanol.org/pdfs/wetmilling.pdfhttp://www.ethanol.org/pdfs/drymilling.pdf


37/76

The major steps in the dry mill process are:

1. Milling. The feedstock passes through a hammermill which grinds it into a fine powder called meal.

2. Liquefaction. The meal is mixed with water and

alpha-amylase, then passed through cookers wherethe starch is liquefied. Heat is applied at this stage toenable liquefaction. Cookers with a high temperaturestage (120-150 degrees Celsius) and a lowertemperature holding period (95 degrees Celsius) areused. High temperatures reduce bacteria levels in themash.


38/76

3. Saccharification. The mash from the cookers is

cooled and the secondary enzyme (gluco-amylase) is

added to convert the liquefied starch to fermentablesugars (dextrose).

4. Fermentation. Yeast is added to the mash to

ferment the sugars to ethanol and carbon dioxide.Using a continuous process, the fermenting mash is

allowed to flow through several fermenters until it is

fully fermented and leaves the final tank. In a batch

process, the mash stays in one fermenter for about 48

hours before the distillation process is started.


39/76

5. Distillation. The fermented mash, now called beer, contains about

10% alcohol plus all the non-fermentable solids from the corn and

yeast cells. The mash is pumped to the continuous flow, multi-

column distillation system where the alcohol is removed from thesolids and the water. The alcohol leaves the top of the final column

at about 96% strength, and the residue mash, called stillage, is

transferred from the base of the column to the co-product

processing area.

6. Dehydration. The alcohol from the top of the column passes

through a dehydration system where the remaining water will be

removed. Most ethanol plants use a molecular sieve to capture the

last bit of water in the ethanol. The alcohol product at this stage is

called anhydrous ethanol (pure, without water) and is approximately

200 proof.

Manufacture of Ethanol


40/76


Ethanol may be produced by either synthetic chemical method or by fermentation.

Fermentation was until about 1930 the main means of alcohol production.

In 1939, for example 75% of the ethanol produced in the US was by fermentation,in 1968 over 90% was made by synthesis from ethylene.

Due to the increase in price of crude petroleum, the source of ethylene used for

alcohol production, attention has turned worldwide to the production of alcohol by

fermentation.

Fermentation alcohol has the potential to replace two important needs currentlysatisfied by petroleum, namely the provision of fuel and that of feedstock in the

chemical industry.

The production of gasohol (gasolinealcohol blend) appears to have received

more attention than alcohol use as a feed stock.

Nevertheless, the latter will also surely assume more importance if petroleum price

continues to ride.


41/76


Governments the world over have set up programs designed to conserve

petroleum and to seek other energy sources.

One of the most widely publicized programs designed to utilize a new

source of energy is the Brazilian National Ethanol Program. Set-up in 1975,

the first phase of this program aims at extending gasoline by blending it

with ethanol to the extent of 20% by volume.

The United States government also introduced the gasoline programme

based on corn fermentation in 1980 following the embargo on grain sales

to the then Soviet Union.

Substrates


42/76

Substrates

The substrate used will vary among countries.

In Brazil sugar cane, already widely grown in the country, is the major

source of fermentation alcohol, while it is planned to use cassava and

sweet sorghum.

In the United States enormous quantities of corn and other cereals

are grown and these are the obvious substrates.

Cassava grows in many tropical countries and since it is high yielding

it is an important source in tropical countries where sugar cane is not

grown.

It is recognized that two important conditions must be met before

fermentation alcohol can play a major role in the economy either asgasohol or as a chemical feedstock.

First, the production of the crop to be used must be available to

produce the crop without extensive and excessive deforestation.

Secondly, the substrate should not compete with human food.

Fermentation


43/76

Fermentation The sterilized fermentable sugars are pumped or allowed to flow by gravity into

fermentation tanks and yeast is inoculated or pitched in at a rate of 7-15 x 106

yeast cells/ml, usually collected from a previous process.

These broths are inoculated with up to 5% (v/v) of thick yeast broth.

Although yeast is re-used there is still a need for regular inocula.

In general the inocula are made of selected alcohol-tolerant yeast strains usually

Sacch. cerevisiae grown aerobically with agitation and in a molasses base.

Progressively larger volumes of culture may be developed before the desiredvolume is attained.

When the nitrogen content of the medium is insufficient nitrogen is added usually

in the form of an ammonium salt.

As in all alcohol fermentations the heat released must be reduced by cooling and

temperatures are generally not permitted to exceed 35-37C. The pH is usually in the range 4.5-4.7, when the buffering capacity of the medium

is high.

Higher pH values tend to lead to higher glycerol formation.

When the buffering capacity is lower, the initial pH is 5.5 but this usually falls to

about 3.5. During the fermentation contaminations can have

Distillation


44/76

Distillation After fermentation the fermented liquor or beer contains alcohol as

well as low boiling point volatile compounds such as acetaldeydes,

esters and the higher boiling, fusel oils. The alcohol is obtained by several operations.

First, steam is passed through the beer which is said to be steam-

stripped.

The result is a dilute alcohol solution which still contains part of theundesirable volatile compounds.

Secondly, the dilute alcohol solution is passed into the center of a

multi-plate aldehyde column in which the following fractions are

separated: esters and aldehydes, fusel oil, water, and an ethanolsolution containing about 25% ethanol.

Thirdly, the dilute alcohol solution is passed into a rectifying column

where a constant boiling mixture, an azeotrope, distils off at 95.6%

alcohol concentration.

Distillation


45/76

Distillation To obtain 200 proof alcohol, such as is used in gasohol blending, the

96.58% alcohol is obtained by azeotropic distillation.

The principle of this method is to add an organic solvent which will forma ternary (three-membered) azeotrope with most of the water, but with

only a small proportion of the alcohol.

Benzene, carbon tetrachloride, chloroform, and cyclohezane may be

used, but in practice, benzene is used. Azeotropes usually have lower boiling point than their individual

components and that of benzene-ethanol-water is 64.6C.

On condensation, it separates into two layers.

The upper layer, which has about 84% of the condensate, has thefollowing percentage composition: benzene 85%, ethanol 18%, water

1%.

The heavier, lower portion, constituting 16% of the condensate, has the

following composition: benzene 11%, ethanol 53%, and water 36%.

Distillation


46/76

Distillation In practice, the condensate is not allowed to

separate out, but the arrangement of plates withinthe columns enable separation of the alcohol. Four

columns are usually used.

The first and second columns remove aldehydes

and fusel oils, respectively, while the last two

towers are for the concentration of the alcohol.

A flow diagram of conventional absolute alcohol

production from molasses is given in Fig. 20.4

ll


47/76

Distillation


48/76


49/76

Ethanol Dry-Grind Grind bushel of corn (56 lb.), add water, make mash,

cook to kill bacteria, expose starch

Add enzymes for flow & to convert starch to sugar

Introduce Yeasts in Batch Fermenters---- produce beer-

--- distill the ethanol

Products:

ethanol(2.75 gal.) requires heat to distill

DDGS- (18 lbs.) generally requires drying CO2-- ( 18 lbs. ) food grade

150 bushel corn yields 413 gallons of ethanol per acre,

2700 pounds of DDGS

Corn

Corn Dry Milling Process Overview


50/76

Corn Dry-Milling Process Overview

Alpha-amylase enzyme

CO2

Yeast and

Gluco-amylase enzyme

Whole Stillage

Thin Stillage

Coars Solids

Feed Industry Co-products

(Source: Kelly Davis, Chippewa Valley Ethanol Company)

Corn Cleaning

Hammermill Mix Slurry Liquefaction

Cooker

Centrifuge Evaporator

Fermentation

Dist illat ion

Ethyl

Alcohol

Conditioned

Distillers

Solubles

Distillers

Dried

Grains with

Solubles

Distillers

et Grains

Rotary Dryer


51/76

7. Denaturing. Ethanol that will be used for fuel must

be denatured, or made unfit for human consumption,

with a small amount of gasoline (2-5%). This is done atthe ethanol plant.

8. Co-Products. There are two main co-products

created in the production of ethanol: distillers grainand carbon dioxide. Distillers grain, used wet or dry, is

a highly nutritious livestock feed. Carbon dioxideis

given off in great quantities during fermentation and

many ethanol plants collect, compress, and sell it for

use in other industries.
http://www.ethanol.org/distillersgrain.htmlhttp://www.ethanol.org/carbondioxide.htmlhttp://www.ethanol.org/carbondioxide.htmlhttp://www.ethanol.org/distillersgrain.html


52/76

Distillers grain can be fed to livestock wet or

dry. Dried distillers grain (DDG)is the most

common variety. Drying the distillers grain

increases its shelf life and improves its ability

to be transported over longer distances. If a

consistent nearby market can be secured,ethanol producers can supply the feed as wet

distillers grain (WDG). The wet form is not as

easily transportable, but the cost of drying theproduct is removed.


53/76

Dried distillers grain with solubles (DDGS)is theform available to the feed industry. The liquid that is

separated from the mash during the distilling processis partially dehydrated into a syrup, then added backonto the dried distillers grain to create DDGS.

DDGS is a high quality feedstuff ration for dairy

cattle, beef cattle, swine, poultry, and aquaculture.The feed is an economical partial replacement forcorn, soybean meal, and dicalcium phosphate inlivestock and poultry feeds. Historically, over 85% ofDDGS has been fed to dairy and beef cattle, and

DDGS continues to be an excellent, economical feedingredient for use in ruminant diets.


54/76

The personal care products industry is one of the largestusers of industrial ethanol, or ethyl alcohol.

Check the labelshairspray, mouthwash, aftershave,

cologne, and perfume all contain large amounts of

alcohol by volume. Ethanol is also used in many

deodorants, lotions, hand sanitizers, soaps, and

shampoos.

R f Eth l b


55/76

Recovery of Ethanol by

Distillation process

Ethanol was recovered by simple distillation

method.


56/76

SugarcaneSource of Green Energy

JUICE

BAGASSE

LEAVES & TOPS

SUGAR

CO-GENERATION

OF ELECTRICITY

Ethanol

Fl h t f S d Eth l


57/76

Flowsheet of Sugar and Ethanol

Production

J

uice


58/76

Ethanol from Molasses and Juice

MASH

JUICE FOR SUGAR

FACTORY

SUGAR

ETHANOL

FROM

SUGARS

SUGARCANE

MILLING

FERMENTATION

DISTILLATIONMOLASSES

JUICE FOR ETHANOL

ETHANOL

FROM

MOLASSES

ETHANOL

DISTILLERY

Sugars = Suc + Glu + Fru


59/76

Milling Diagram

Usina Santo Antonio S. A. - Fluxograma de Processo - Setor de moendas

gua de

emb ebio

Tanque Pulmo

Peneira

Rotativa

Trocador de calor

regenerativo

Tanque de

cido

FosfricoCaldoclarificadopara

destilaria

Bagacilhopara lodo

dos decantadores

Circuito acar

Circuito lcool

Eletro-Im

Vinha a

(Entrada)

Vinha a

(Sada)Caldoclarificadodo

decantador de lcool

Caldodocircuitolcool

para os trocadores de calor

LegendaCaldo de cana

guas industriais

Bagao

Produtos qumicos

Bagaopara as

caldeiras

Caldodocircuitoacar

para a sulfitao

Cana

gua de lavagem de cana

Picador 01

Picador 02

Estei ra de cana picada

Mesa 18 - cana intei ra

Bagao da penei ra

Desfr ibador

Rolo al imentador

Espalhador


60/76

FERMENTATION PROCESS

The medium is inoculated with a suspensionof conidia of Penicillium chrysogenum.

The medium is constantly aerated and

agitated, and the mould grows throughout aspellets.

After about seven days, growth is complete,the pH rises to 8.0 or above, and penicillinproduction ceases


61/76

STAGES IN DOWNSTREAM PROCESSING

Removal of cells

The first step in product recovery is the

separation of whole cells and other insoluble

ingredients from the culture broth by

technique such as filtration and

centrifugation.

ISOLATION OF BENZYL PENICILLIN


62/76

ISOLATION OF BENZYL PENICILLIN

The PH is adjusted to 2-2.5 with the help of phosphoric or sulphuricacids.

In aqueous solution at low PH values there is a partition coefficient infavor of certain organic solvents such as butyl acetate.

This step has to be carried out quickly for penicillin is very unstable at

low PH values. Antibiotic is then extracted back into an aqueous buffer at a PH of 7.5,

the partition coefficient now being strongly in favor of the aqueousphase. The resulting aqueous solution is again acidified & re-extractedwith an organic solvent.

These shifts between the water and solvent help in the purification ofpenicillin.


63/76

The treatment of the crude penicillin extract varies according to theobjective, but involves the formation of an appropriate penicillinsalt.

The solvent extract recovered in the previous stage is carefullyextracted back with aqueous sodium hydroxide.

This is followed by charcoal treatment to eliminate pyrogens and bysterilization.

Pure metal salts of penicillin can be safely sterilized by dry heat, ifdesired. Thereafter, the aqueous solution of penicillin is subjectedto crystallization.


64/76

FURTHER PROCESSING

For parental use, the antibiotic is packed in sterile vials asa powder or suspension.

For oral use, it is tabletted usually now with a film

coating.

Searching tests (ex: for purity, potency) are performed

on the appreciable number of random samples of the

finished product.

It must satisfy fully all the strict government standardsbefore being marketed

The main stages of Penicillin production


65/76

The main stages of Penicillin production

are:


66/76


67/76

PRODUCTION OF PENICILLIN V


68/76

PRODUCTION OF PENICILLIN V

Phenoxy methyl penicillin Addition of different Acyl groups to the

medium.

Phenoxyacetic acid as precursor instead ofphenyl acetic acid.


69/76

When penicillin was first made at the end ofthe second world war using the fungusPenicilium notatum, the process made 1 mgdm-3.

Today, using a different species (P.

chrysogenum) and a better extractionprocedures the yield is 50 g dm-3.

There is a constant search to improve the

yield.


70/76

Antibiotics can be selectively toxic by

targeting such features as the bacterial cellwall, 70S ribosomes, and enzymes that are

specific to bacteria.

In this way the human eukaryotic cells are

unaffected.


71/76

For example:

penicillin, ampicillin, amoxycillin, methicillin

Inhibits enzymes involved in synthesis of

peptidoglycan for bacterial cell wall, causing

cell lysis.

Bacteriocidal

Narrow spectrum- little effect on Gram

negative cells.

Downstream processing is relatively easy


72/76

Downstream processing is relatively easysince penicillin is secreted into the medium(to kill other cells), so there is no need tobreak open the fungal cells.

However, the product needs to be very pure,since it being used as a therapeutic medicaldrug, so it is dissolved and then precipitatedas a potassium salt to separate it from other

substances in the medium.


73/76


74/76

h l ll ( ll d ll )


75/76

The resulting penicillin (called penicillin G)

can be chemically and enzymatically

modified to make a variety of penicillins withslightly different properties.

These semi-synthetic penicillins includepenicillin V, penicillin O, ampicillin and

amoxycillin.

1. What is the Carbon source?

2 What is the nitrogen source?lactose

yeast


76/76

2. What is the nitrogen source?

3. What is the energy source?

4. Is the fermentation aerobic or anaerobic?

5. What is the optimum temperature?

6. Is penicillin a primary or secondary metabolite?7. What volume fermenter is used?

8. Why isn't a larger fermenter used?

9. When is penicillin produced?

10. How long can it be produced for?

11. What was the first fungus known to produce penicillin?

12. What species produces about 60mg/dm3 of penicillin?13. How did scientists improve the yield still further?

14. What is the substrate?

15. Why is batch culture used?

16. What are the processes involved in down-stream processing?

a)

b)c)

17. Why can't penicillin be taken orally?

18. Name the form of penicillin which can be taken orally.

19. How does Penicillin kill bacteria?

yeastglucose

aerobic

25 - 27C

secondary40200 dm3

To difficult to aerate

40 hoursafter main increase in fungal mass

140 hours (18040 hours)

Penicillin notatum

Penicillin chrysogenumGenetic modification

Corn steep liquor

Secondary metabolite

Filtration of liquid

Extraction from filtrate by counter current of butylacetatePrecipitation by potassium salts

Destroyed by stomach acid

Penicillin V, ampicillin

Stops production of cell wall

dsp of some prdts vii sem

Documents