29-Jan-18

Welcome !!
BIOCHEMICAL
ENGINEERING
CHE F 421

Instructor-in-charge:
DR. AMIT JAIN

Research Areas
• Process Control & Instrumentation
– Decentralized Control of Multivariable systems
• Applications to Bioprocess Systems
• Process and Plant Safety
– Design and Analysis of Pool Fire Suppressants
– CFD Applications in Process Safety Systems
• Biochemical Engineering
– Bioremediation of Waste Automobile Engine Oil
– Biosurfactant: Production, Recovery and Characterization

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 2

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Scope & Objective

• To provide a general understanding of the basic
concepts of
- microbiology
- enzyme-catalysis
• To apply chemical engineering principles to
- bioreactor analysis
- downstream processing
- application to wastewater treatment

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 3

Scope & Objective

• To accommodate those students who do not have the
biological background, the course will first introduce
the basic concepts from microbiology, biochemistry,
and the central dogma of biology.
• Subsequently, the emphasis will be on the application
of the principles of chemical engineering to biological
processes.

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 4

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Engineers Vs Scientist

• Scientist strive to create new knowledge about how

things work.
• Engineers understand well the tools science and
mathematics provide, and utilize them to solve
problems for public and economic gain.

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 5

Definitions
• Biochemical engineering: has usually meant the
extension of chemical engineering principles to
systems using a biological catalyst to bring about
desired chemical transformations.

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 6

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Definitions
• Biotechnology
- Traditionally, implies the use or development of
methods of direct genetic manipulation for a socially
desirable product.

- Broadly, “Commercial techniques that use living

organisms, or substances from those organism, to
make or modify a product…”
(Congress of the United States, 1984)

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 7

Definitions
Fermentation
CH₃CHCOOH

- Traditionally, defined as the process for the

production of alcohol or lactic acid from glucose.
- Broadly, defined as “an enzymatically controlled
transformation of organic compound”
(Webster’s New College Dictionary)

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 8
C6H12O6

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Typical Bioprocess

Stock culture Raw materials Medium

Microorganism preparation
cell preparation Shake flask Medium formulation

Seed fermenter Sterilization

Production fermenter Computer control

Air

Recovery

Purification Products

Effluent treatment
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 9

Batch Fermenter
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 10

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29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 11

Biochemical Engineering History

• 5000 to 10,000 BC:
yogurt, cheese and soy products, wine and beer.

• In early 20th century:

pure bakers yeast were being produced in tanks and
sold, antibiotics production began on the
commercial scale.

• 1970s:
Recombinant DNA technology: Molecular level
manipulation of DNA in a purposeful and
predetermined manner.
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 12

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The Future
• Intellectual revolution emerge new visions and
hopes:
– Semi-synthetic organs grown in large vats
– Abundant and nutritious food
– Computers based on biological molecules rather than
silicon chips
– Super-organisms to degrade pollutants
– Consumer products and industrial processes
• Typically, the living organisms obeys the rules of
chemistry and physics and are predictable. Thus,
the processes to use them can be rationally
constructed on commercial scale.
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 13

Role of Biochemical Engineers

• A biochemical engineer takes a recipe that has
been formulated by a biologist or a chemist in
the laboratory and develops it into a large-scale
manufacturing process.
• Biochemical engineers design the manufacturing
equipment that is required to convert raw
materials into the products that you have at
home, like cold tablets and packaged foods.
• If you are interested in applying your problem-
solving skills to improve human lives, then you
should definitely investigate this career.

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 14

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TEXT BOOK
• TB: "Biochemical Engineering Fundamentals" by James E.
Bailey and David F. Ollis (2011) 2nd Ed. McGraw Hill
International Edition.
REFERENCE BOOKS:
• R1: "Bioprocess Engineering: Basic Concepts" by Michael L.
Shuler and Fikret Kargi (2005) Third Indian Reprint, Pearson
Education.
• R2: "Biochemical Engineering" by Harvey W. Blanch & Douglas
S. Clark (1997), Marcel Dekker, Inc., New York.
• R3: "Coulson and Richardson's Chemical Engineering", Vol. 3
by J F Richardson and D G Peacock, 3rd Ed., Asian Books
Private Limited, New Delhi.
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 15

EVALUATION SCHEME

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 16

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NOTE
• Make-up would only be granted under special
conditions as per the institute policy with prior
permission from I/C.
• Chamber Consultation Hour:
Saturday 11:30 AM -12:00 Noon.
• Notices: To be displayed on the chemical engineering
notice board and on Nalanda.

29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 17

History of Penicillin
• In 1928, Alexander Fleming at St. Mary’s Hospital, London
was trying to isolate the bacterium, Staphylococcus aureus by
growing it on the surface of nutrient.
• He noticed that no bacteria grew near the invading substance in
the contaminated plate:
Meaningful finding, not a failed experiment
• He thought the cell killing must be due to an antibacterial agent.
• Identification of foreign particles as common mold of the
Penicillium genus (later identified as Penicillium notatum)
• Recovery of a tiny quantity of secreted material (named
“Penicillin”) using the crude extraction methods.
• The discovery laid essentially dormant for over a decade
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 18

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29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 19

Penicillin Story
• World War II resurrected the discovery : desperate demand for
an antibiotic with minimal side effects and broad applicability.
• Howard Florey and Ernst Chain of Oxford : rebuilt on
Fleming’s observation.
• They produced enough penicillin to treat some laboratory
animals.
• Treatment of a London bobby for a blood infection great
efficacy against infection
• The supply of penicillin was exhausted and person died.
• Need a process to make large amounts of penicillin
• Process development required engineers, microbiologists, and
life scientists.
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 20

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Penicillin Story
• First attempt : chemical synthesis of penicillin because of a
great deal of success with other drugs
Chemical synthesis: proved to be extremely difficult.
Fermentation process: an unproved approach.
• Decision taken on the commercial production of penicillin by a
fermentation process.
• Problems
– Very low concentration (titer) of penicillin in broth : ~0.001 g/L (1 ppm)
– Low rate of production per unit volume
– Very large and inefficient fermentors
– Fragile and unstable penicillin
– Very difficult in product recovery and purification
• The Enchanted Ring: The Untold Story of Penicillin by John Sheehan
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 21

Penicillin Story
• Major contribution to the penicillin program by Northern
Regional Research Laboratory (NRRL)
• Development of a corn steep liquor-lactose based medium
 ten-fold increased productivity
• Isolation of a new strain (> few hundreds) : Penicillium
chrysogenum
• The other hurdle : Manufacturing process
- growth of the mold on the surface of moist bran
- growth of the mold on top of a liquid medium ; requires
large number of
milk bottles  Bottle plant  long growing cycle and
labor intensive
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 22

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• Submerged fermentation process : Challenges

– Mold physiology : productivity vs conditions
– Reactor design : reactor size and configuration, oxygen supply
(viscosity, mixing, mass transfer ), heat removal, agitator design,
mechanical sealing, decontamination,
– Product recovery/purification : A combination of pH shift and
liquid-liquid extraction
• First plant for commercial production by Pfizer (100,000 gal
scale) in 1985.
• Accomplishment required a high level of multidisciplinary
work. Ex. Merck assigned a engineer and microbiologist
together to each aspect of the problem
• Continued progress with penicillin fermentation through
physiology, metabolic pathway engineering, mold genetics,
process control, reactor design: Starting with 0.001,
reaching ~ 100 g/L
29-Jan-18 Dr. Amit Jain, Assistant Prof., Dept. of Chemical Engg., BITS Pilani 23

Thanks for your patience !!

To be continued….

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