CHE 475

Biochemical Engineering II

Shoeb Ahmed, PhD

Assistant Professor
Chemical Engineering Department
Bangladesh University of Engineering and Technology

April 2nd, 2018

Course Syllabus
CHE 475: Biochemical Engineering II
COURSE SYLLABUS: January 2018

Instructors:
Shoeb Ahmed, PhD Nafisa Islam, PhD
shoebahmed@che.buet.ac.bd nafisaislam@che.buet.ac.bd
http://shoebahmed.buet.ac.bd

Class meets: Monday 12:00-12:50, Room 255, OAB

Tuesday 10:00-10:50, Room 255, OAB
Wednesday 12:00-12:50, Room 255, OAB

© 2013-16 Shoeb Ahmed, PhD

 Course Syllabus
CHE 475: Biochemical Engineering II
COURSE SYLLABUS: January 2018

Course Learning Outcomes:

Upon completion of the course, students will be able to:

• Comprehend the meaning of the terminology and physical phenomenon associated
with Biochemical Engineering and Biotechnology.
• Understand the transport phenomena in the bioreactor systems.
• Identify downstream bioprocessing need for any bioprocess industries.
• Acquire knowledge on different aspects of biosensing technology.
• Deal with cutting edge bioengineering concepts such as recombinant DNA
technology, Intracellular signaling and so on.

© 2013-16 Shoeb Ahmed, PhD

Course Syllabus
• Biochemical Engineering I: Recap
– Microorganisms, Biomolecular building blocks,
– Microbial growth phases and kinetics
– Enzyme kinetics
• Bioreactor and Biorefinery
– Applications of Bioreactors
– Bioreactor configurations
– Ideal bioreactors based on modes of operation
– Practical aspects to be considered
• Biosensors
– Classifications, parts of biosensors
– Transducing mechanism
– Specialized equipment for biosensors
• Class test 1
© 2013-16 Shoeb Ahmed, PhD
 Course Syllabus
• Mass transfer and transport phenomena in Bioreactor
– Gas liquid mass transfer in cellular systems
– Determination of oxygen transfer rates
– Factors affecting oxygen demand and transfer rate
• Scaling up of the lab process
• Class test 2
• Downstream bioprocessing
– Separation and recovery of purified product
– Basic separation units
• Protein Purification
– IEX
– HIC
– Affinity
• Class test 3
© 2013-16 Shoeb Ahmed, PhD

Course Syllabus
• Special topics:
– Quality Assurance in pharmaceutical industries
– Recombinant DNA technology
– Cell Signaling
– Imaging and Image analysis in life science
• Class test 4

© 2013-16 Shoeb Ahmed, PhD

 Course Syllabus
Recommended books:

Bailey, J., Bailey, J., Ollis, DF. Biochemical

Engineering Fundamentals. McGraw-Hill,
1986. ISBN-10: 0070032122; ISBN-13: 978-
0070032125

Doran, PM. Bioprocess Engineering

Principles. Academic Press, 2012. ISBN-10:
012220851X; ISBN-13: 978-0122208515

Shuler, ML. and Kargi, F. Bioprocess

Engineering: Basic Concepts. Prentice Hall,
2001. ISBN-10: 013081908; ISBN-13: 978-
0130819086

Doble, M. and Gummadi, SN. Biochemical

Engineering. Prentice Hall, India, 2007.
ISBN-978-81-203-3052-8.

© 2013-16 Shoeb Ahmed, PhD

Course Syllabus
Grading: (If not changed by BUET)

Attendance: 10% of total grade

Class test/Assignment (minimum 4): 20% of total grade
Final Exam (comprehensive): 70% of total grade
Final grades might be curve-fitted for better distribution.

© 2013-16 Shoeb Ahmed, PhD

 How big is a cell?

© 2013-16 Shoeb Ahmed, PhD

How big is a cell?

Image : http://www.phschool.com/science/biology_place/biocoach/cells/common.html

© 2013-16 Shoeb Ahmed, PhD

 Antibody

© 2013-16 Shoeb Ahmed, PhD

Antibody

© 2013-16 Shoeb Ahmed, PhD

 Enzyme
• All proteins bind to other molecules.

• Enzyme is a kind of protein that binds

different substrates.

• Enzymes are powerful and highly specific

catalysts.

© 2013-16 Shoeb Ahmed, PhD

Enzyme

© 2013-16 Shoeb Ahmed, PhD

 Prokaryotic cell
Prokaryotes are the most diverse and numerous single-celled organism on earth.
Example of prokaryotes is bacteria.

These cells lack a membrane-bound nucleus.

Prokaryotic cells have various shapes.

© 2013-16 Shoeb Ahmed, PhD

Eukaryotic cell
The primary distinguishing feature of eukaryotes is the existence of an internal
membrane separating the DNA from the remainder of the cytoplasm.

The DNA in eukaryotes is generally organized in one or more long chains called
chromosomes.

Most of the familiar organisms are eukaryotes. Single celled organisms like yeast,
and amoebae, plants, animals all are eukaryotes.

© 2013-16 Shoeb Ahmed, PhD

 Average Composition of Bacteria

© 2010 Nature Education. All rights reserved

Cell wet weight = 4-5 times cell dry weight

© 2013-16 Shoeb Ahmed, PhD

Biomolecular Building Blocks

© 2013-16 Shoeb Ahmed, PhD Figure 2-32 Molecular Biology of the Cell (© Garland Science 2008)
 Biomolecular Building Blocks

© 2013-16 Shoeb Ahmed, PhD Figure 2-17 Molecular Biology of the Cell (© Garland Science 2008)

Biomolecular Building Blocks

A DNA molecule consists of two complementary chains of nucleotides.
The structure of DNA provides a mechanism for heredity.

Each nucleotide is composed of a

nitrogen-containing nucleobase—
either guanine (G), adenine (A),
thymine (T), or cytosine (C)—as well
as a monosaccharide sugar called
deoxyribose and a phosphate group.

© 2013-16 Shoeb Ahmed, PhD

 Biomolecular Building Blocks
Proteins are large biological molecules, consisting of one or more long
chains of amino acid residues.

Amino acids are composed of

amine (-NH2) and carboxylic acid
(-COOH) functional groups, along
with a side-chain specific to each
amino acid.

© 2013-16 Shoeb Ahmed, PhD Collected from the web

Biomolecular Building Blocks

© 2013-16 Shoeb Ahmed, PhD

 Central Dogma of Biology

© 2013-16 Shoeb Ahmed, PhD

Enzyme Kinetics

Michaelis–Menten equation: Reaction rate,

where,

© 2013-16 Shoeb Ahmed, PhD

 CHE 475
Biochemical Engineering II

Shoeb Ahmed, PhD

Assistant Professor
Chemical Engineering Department
Bangladesh University of Engineering and Technology

April 3rd, 2018

Biocatalyst Organism
• The microorganisms are provided with everything they need to
grow and reproduce.

Saccharomyces cerevisiae
Benefits: (5-10 µm)
• Very inexpensive
• Easy to maintain
• Very high yield
• Simple mode of nutrients transportation
• Metabolic diversity
• High genetic adaptability

Escherichia Coli (0.5-1 µm)

© 2013-16 Shoeb Ahmed, PhD Collected from the web
 Microbial Growth kinetics

© 2013-16 Shoeb Ahmed, PhD

Microbial Growth Phases

Lag Phase – Cells adapt to a new environment; no or very little
growth.

Acceleration phase: Growth starts

Exponential Phase – Rapid growth
by cell division characterized by
maximum growth rate.

© 2013-16 Shoeb Ahmed, PhD

 Microbial Growth Phases
Decline phase: Growth rate slows due to nutrient exhaustion or
accumulation of toxic products
Stationary Phase – Cells remain viable and productive. Balanced
cell growth and cell death.

Death Phase – Significant cell lysis

and death, characterized by a
death rate constant

© 2013-16 Shoeb Ahmed, PhD

Microbial Growth Kinetics

During the exponential growth phase in a batch fermenter:

x  x0e t x = number of viable cells

1 dx
Specific growth rate,   µmax = max. specific growth rate
x dt

ln 2
Doubling time, tD =


How to get µ from cell growth data?

How to calculate the lag period?

© 2013-16 Shoeb Ahmed, PhD Collected from the web

 Microbial Growth Kinetics
During the death phase in a batch fermenter:

x  x0e(  kd ) t

kd = Specific death rate constant

Measurement of biomass:
Optical density:
Based on turbidity;
Counts both dead and live cells along with other compounds
Cell count:
Slow process, but counts only cells;
Possible to count only viable cells too
© 2013-16 Shoeb Ahmed, PhD

Monod’s Growth kinetics

Specific growth rate (µ) depends on the nutrient concentration (S)

max S KS = half saturation constant


KS  S Where, µ = 0.5µmax

If µ depends on the nutrient

concentration (S), then how is it
considered same for a system?

In reality, S >>> KS
Thus, µ ≈ µmax
(Follows exponential kinetics)

© 2013-16 Shoeb Ahmed, PhD

Valid as long as S > 10KS
 Monod’s Growth Kinetics
max S
 What happens when nutrient is
KS  S consumed to a level <10KS

There is an abrupt transition

from exponential growth phase
to stationary phase.

Monod’s model is applicable for balanced growth without significant

change in growth conditions.

© 2013-16 Shoeb Ahmed, PhD

Microbial Growth Kinetics

During the stationary phase, yield in terms of nutrient and
microbial mass:

dx
Yx / s  
dS
Yx / s ( S0  S )  x  x0
x  x0  S0Yx / s [at stationary phase S ≈ 0
 S0Yx / s at time=0, x0 ≈ 0]

Exponential growth Stationary phase Death phase

x  x0e t x  x0  S0Yx / s x  x0e(  kd ) t

© 2013-16 Shoeb Ahmed, PhD

 Continuous Fermenter
dx
 Fx0  Vx  Fx
dt

At steady state, net accumulation, dx  0

dt
Amount of cell at stating point (x0) is negligible

F
 D
V

Continuous cultures are used to fix the growth rate.

At steady state, S 
DK S  DK S 
; x  YX / S  S0  
max  D  max  D 

© 2013-16 Shoeb Ahmed, PhD

‘Washout’ Condition
max S F
  D
KS  S V

It is necessary to increase both D and X to increase

the productivity of fermentation.

However, there is a maximum limit of dilution rate,

beyond that value cells will be washed out.

© 2013-16 Shoeb Ahmed, PhD

 ‘Washout’ Condition
max S F
  D
KS  S V

It is necessary to increase both D and X to increase

the productivity of fermentation.

However, there is a maximum limit of dilution rate,

beyond that value cells will be washed out.
 max S o
Dmax 
K S  So

© 2013-16 Shoeb Ahmed, PhD

‘Washout’ Condition
max S F
  D
KS  S V

It is necessary to increase both D and X to increase

the productivity of fermentation.

However, there is a maximum limit of dilution rate,

beyond that value cells will be washed out.
 max S o
Dmax 
K S  So

Dmax  D For D > Dmax, there will be “washout”, no steady-

state.
© 2013-16 Shoeb Ahmed, PhD