Biochemical Engineering

CHE F421

VIVEK R BITS Pilani, K K Birla Goa Campus

 BIOCHEMICAL ENGINEERING

Petrochemical Engineering

Environmental
engineering

Materials science and technology

Pharmaceutical Technology

Electrochemical Engineering
Chemical Engineering

Food Technology

Paint& Textile Technology

Membrane separation processes

Polymer science and technology

 Biochemical Engineering – An overview

 Biochemical engineering may be defined as the use of microorganisms, or part of them,

for the production of chemical or biological materials or the development of new

processes.

 With chemical engineering as its core, biochemical engineering also embraces aspects of

biochemistry, cell and molecular biology, bioorganic and bioinorganic chemistry.

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 Schematic diagram for penicillin production

Yes, it’s a chemical engineer’s job

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VIVEK R BITS Pilani, K K Birla Goa Campus
Important human activities

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Art  Science  Technology

Sheep Rearing 13000 BC

Animal Husbandry
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Art  Science  Technology

Agriculture 9500 BC

Agriculture Science and Technology

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Art  Science  Technology
Wine making 6000 BC

Wine Biotechnology
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Antonie van Leeuwenhoek

Discovered single-celled protists

Named as “Animacules”

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Natural growth Vs Controlled growth

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 Animals, Plants  Eukaryotes  Difficult to tune up as a whole (-) (Climate dependent)

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Animal cells Plant cells  controlled growth ( )

Growth in
Yeast cells Mould cells  controlled growth ( ) Bioreactors

Bacterial cells  controlled growth ( )

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 Bioreactors
Microorganisms

Nutrients
Product

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Modeling the reaction system

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 Lab scale Lab scale

 Medium
 Inoculum
 Temperature
 Kinetics, process????
 pH, Temp
 Process parameters
Bioprocess Optimization
Pilot scale
Industrial scale

 Process parameters
 Energy input
 Scale ↔ processes
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 Biochemical Engineering – An overview

 Biochemical engineering may be defined as the use of microorganisms, or part of them,

for the production of chemical or biological materials or the development of new

processes.

 With chemical engineering as its core, biochemical engineering also embraces aspects of

biochemistry, cell and molecular biology, bioorganic and bioinorganic chemistry.

VIVEK R BITS Pilani, K K Birla Goa Campus

Animal cells Plant cells  controlled growth ( )

Growth in
Yeast cells Mould cells  controlled growth ( ) Bioreactors

Bacterial cells  controlled growth ( )

VIVEK R BITS Pilani, K K Birla Goa Campus

Chemical engineering Vs Biochemical Engineering

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Two parallel worlds connected by biological sciences

Chemical Engineering Bio-chemical Engineering

Microbiology
Biochemistry
Molecular Biology
Recombinant DNA Technology

VIVEK R BITS Pilani, K K Birla Goa Campus

 Two parallel worlds connected by biological sciences

Chemical Engineering Bio-chemical Engineering

Microbiology
Biochemistry
Molecular Biology
Recombinant DNA Technology
Reactions and Separations  Higher tempReactions and Separations  low temp

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The discovery of Penicillin  Industrial Production

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 Isolation of bacterial inhibiting mould

Flemming’s own photograph

Alexander Flemming, 1928 St Mary’s Hospital London
of original mould
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With antibiotic Without antibiotic

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Penicillin discovery

Penicillium Penicillin

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 Penicillin production in shake flasks

Submerged fermentation Solid-state fermentation

1938
Howard Florey, Ernst Chain, Oxford university

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Small scale penicillin production at UK

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 Industrial scale production of penicillin

First pilot-scale Penicillin production, NRRL, US

First commercial plant, Pfizer 1944 US
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 Scaling up production
Issues
 Low yield (1 mg/L)

 Poor understanding of bio-production processes

 Poor understanding of downstream processing

 Contamination

 Low oxygen transfer

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Chemical engineers’ contribution

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 Improvements in production: Chemical engineers’ contributions

 New production medium based on cornsteep liquor and lactose

 Use of antifoaming agent
50,000 folds
 Use of improved agitator and aerator designs
 Improved oxygen transfer raters 50 g/L
 Improved heat transfers
 Use of precursor like phenyl lactic acid
 Improved purification procedures
0.001 g/L
 New Penicillium strain
 Mutation with x-rays and UV-rays

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 Schematic diagram for penicillin production

Yes, it’s a chemical engineer’s job

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 Fermentor design specification sheet

Ghasem,2007 VIVEK R BITS Pilani, K K Birla Goa Campus

 Fermentor design specification sheet

Ghasem,2007 VIVEK R BITS Pilani, K K Birla Goa Campus

Indian Biotechnology Market

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 Top 20 Biopharma companies in India

Biospectrum June 2019

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 Biotech market in India

 Over 800 companies

 3 % global share
 US$ 11 bn against $36.7 bn pharma
 12th among the world
 3rd in Asia
 2nd highest number of USFDA plants
 Largest producer of rec. hepatitis B vaccine
Vision: $100 billion industry by 2025

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https://www.ibef.org/industry/biotechnology-india.aspx
 Bio-Sector categorization

Biopharma: Biopharmaceuticals are generally proteins, drugs and antibodies that are used for
diagnostics and therapeutics.
Bioindustrial: Bioindustrial sector is related to enzymes, yeast and yeast-based products and
organic amino acids.
Bioservices: Bioservices refers to research-based contract, manufacturing contracts and clinical
research contracts.
Bioagri: Bioagri sector is related to biofertilisers, biopesticides and genetically modified seeds.
Bio-IT: This sector is related to different products and services that represent bioinformatics.

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VIVEK R BITS Pilani, K K Birla Goa Campus
 Industrial products produced by biological process

Najafpour 2007 VIVEK R BITS Pilani, K K Birla Goa Campus

Recombinant therapeutics approved for marketing in India

S. Molecules Therapeutic indications

No.
1. Human insulin Diabetes
2. Erythropoietin Anemia
3. Hepatitis B vaccine Hepatitis B
(recombinant surface antigen based)
4. Human growth hormone Deficiency of growth hormone in children
5. Interleukin 2 Renal cell carcinoma
6. Interleukin 11 Thrombocytopenia
7. Granulocyte Colony Stimulating Factor Chemotherapy induced neutropenia
(GCSF)
8. Granulocyte Macrophage Colony Chemotherapy induced neutropenia
Stimulating Factor (GMCSF)

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9. Interferon-2a Chronic myeloid leukemia
10. Interferon-2b Chronic myeloid leukemia, Hepatitis B and
Hepatitis C
11. Interferon-g Chronic granulomatous disease and severe
malignant osteopetrosis
12. Streptokinase Acute myocardial infarction
13. Tissue Plasminogen Activator Acute myocardial infarction
14. Blood factor VIII Haemophilia type A
15. Follicle stimulating hormone Reproductive disorders
16. Teriparatide (Forteo) Osteoporosis
17. Drotrecogin (Xigris) alpha. Severe sepsis
18. Platelet Derived Growth Factor (PDGF) Bone marrow induction and osteoblasts
proliferation
19. Epidermal Growth factor (EGF) Mitogenesis and organ morphogenesis
20. Eptacogalpha (r-F VIIa) r-coagulation Haemorrhages, congenital or acquired
factor hemophilia
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 Bio-manufacturing process

Upstream Fermentation Downstream

Sterile Preparation Production in Purification

-medium fermentor
-Inoculum
-vessel etc.,

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Role of biochemical/bioprocess engineer

1. To obtain the best biological catalyst (microorganism, animal cell, plant cell or enzyme) for a
desired process
2. To create the best possible environment for the catalyst to perform by designing the
bioreactor and operating it in the most significant way
3. To separate the desired products from the reaction mixture in the most economical way

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The basic questions to be asked for process development and design

1. What changes can be expected to occur?

Understanding of microbiology, biochemistry, molecular biology, genetics.

2. How fast will the process take place?

Chemical reaction engineering, thermodynamics, transport phenomena, biological interactions

3. How can the system be operated and controlled for the maximum yield?
Process control and instrumentation

4. How can the products be separated with maximum purity and minimum costs?
Separation techniques
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 Biological processes

Advantages
 Mild reaction conditions
 Specificity Disadvantages
 Effectiveness  Complex product mixtures
 Renewable resources  Dilute aqueous environments
 Recombinant DNA technology  Contamination
 Variability

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Products produced through microbial routes
 Statins
 Xanthan gum
 Rec-Human Insulin
 Probiotics
 Ampicillin
 Vaccine
 Pectinase

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Statins: Cholesterol -lowering agent

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 Cholesterol

Lovastatin, Pravastatin, Simvastatin

Fungal strains produce statins: example- Aspergillus terreus

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Statins  competitive inhibitors of HMG-CoA reductase

(3-hydroxy-3-methylglutaryl-coenzyme A)

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Statins  competitive inhibitors of HMG-CoA reductase
HMG-CoA
Statins
HMG-CoA
reductase
Statins

HMG-CoA
reductase

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Xanthan gum- A Thickening agent

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Hetero Polysaccharide Synthesized by Xanthomonas campesteris

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Enhanced Oil Recovery (EOR)

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