ChE 515

Fundamentals of
Biochemical Engineering

Evelyn B. Taboada, PhD, LLM

Department of Chemical Engineering
University of San Carlos, Cebu City
First Semester, AY 2011-2012

Department of Chemical Engineering

University of San Carlos

Course Outline
Section 1. Introduction to living systems
Chapter 1 Introduction
1.1. Biochemical Engineering
1.2. Biotechnology
1.3. Biological Process
1.4 Definition of fermentation
1.5 History of biotechnology
Chapter 2 Cell cultivation
2.1. Microbial cell cultivation
2.2. Animal cell cultivation
2.3. Plant cell cultivation
2.4. Cell growth measurements

Department of Chemical Engineering

University of San Carlos

Course Outline
Section 1. Introduction to living systems
Chapter 3 Chemicals of Life
3.1. Polysaccharides
3.2. Lipids
3.3. Nucleotides to RNA and DNA
3.4. Amino acids to Proteins
Section 2. Cell kinetics and fermenter design
Chapter 4.1. Introduction and definition of terms
4.2. Growth cycle for batch cultivation
4.3. Stirred-tank fermenter
4.4. Ideal continuous stirred-tank fermenter
4.5. Multiple fermenters connected in series
4.6. CSTF with cell recycling
4.7. Alternative fermenters
3

Department of Chemical Engineering

University of San Carlos

Course Outline
Section 3. Enzyme Technology
Chapter 5.1. Introduction to enzymes
5.2. Simple enzyme kinetics
5.3. Enzyme reactor with simple kinetics
5.4. Inhibition of enzyme reactions
5.5. Other influences of enzyme activity
5.6. Industrial applications of enzymes
Section 4. Downstream processing and other aspects
of bioprocesses
Chapter 6. Immobilization
6.1. Immobilized enzymes and cells
6.2. Immobilization techniques
6.3. Industrial processes applying immobilization
Department of Chemical Engineering
University of San Carlos

Course Outline
Section 4. Downstream processing and other aspects
of bioprocesses
Chapter 7. Sterilization, aeration, and agitation
7.1. Sterilization methods
7.2. Aeration methods and requirements
7.3. Agitation
Chapter 8. Downstream processing
8.1. Introduction to downstream processing
8.2. Solid-liquid separation
8.3. Cell rupture
8.4. Basic recovery and purification methods

Department of Chemical Engineering

University of San Carlos

Grading System
Long exams
Midterm/Final exams
Exercises
Problem sets and assignments
Total

Department of Chemical Engineering

University of San Carlos

50%
40%
5%
5%
100%

Schedule of Exams
First long exam
Second long exam

July 5
July 28

Pointers/Coverage
Section 1: Chap 1-2
Sections 1 and 2

Mid-term exam

Aug 9 or 11

Sections 1 and 2

Third Long exam

Fourth Long exam
Fifth long exam

Aug 30
Sept 15
Sept 29

Section 2 and 3
Section 2 and 3
Section 4

Final exam

Oct 11 or 13 All sections

Department of Chemical Engineering

University of San Carlos

Bibliography
9 Blanch HW and Clark DS. Biochemical Engineering. 1996
9 Doran PM. Bioprocess Engineering. 1995
9 Lee J. Biochemical Engineering. 1995
9 Lee BH. Fundamentals of Food Biotechnology. 1996
9 Belter et al. Bioseparations. 1988
9 Schlegel HG. General Microbiology. 1993
9 Bailey JM & Ollis D. Biochemical engineering fundamentals. 1986

Department of Chemical Engineering

University of San Carlos

Introduction
of
Basic Concepts

Department of Chemical Engineering

University of San Carlos

Do you know what role Biotechnology play

in these products?

Department of Chemical Engineering

University of San Carlos

10

BIOTECHNOLOGY

The Driving Force!

What is biotechnology?

11

Department of Chemical Engineering

University of San Carlos

Biotechnology
is the commercial techniques that use living organisms,
or substances from those organisms, to make or modify a
product, including techniques used for the improvement of
the characteristics of economically important plants and
animals and for the development of micro-organisms to act
on the environment.
the integrated use of biochemistry, microbiology, and
chemical engineering in order to achieve the technological and
industrial application of the capacities of micro-organisms and
cultured tissue cells.

Department of Chemical Engineering

University of San Carlos

12

Biochemical Engineering
is concerned with conducting biological processes on an
industrial scale.

Bioprocess Engineering
is the application of chemical engineering principles to
effect desirable chemical conversions using living cells,
sub-cellular organelles, or enzymes.
typically, such processes involve reactors containing
biological catalysts followed by product recovery sections.
13

Department of Chemical Engineering

University of San Carlos

Bioengineering discipline
Biological
Engineering

Biomedical
Engineering

Biochemical
Engineering
Biomolecular
Engineering

Bioprocess
Engineering

efficient and effective

bio-products and bio-services
Department of Chemical Engineering
University of San Carlos

14

General Introduction

Delft

1650s: Antony van Leeuwenhoek

- first to observe and accurately
record and report microorganisms.

Antony van Leeuwenhoek (1632-1723)

15

Department of Chemical Engineering

University of San Carlos

General Introduction
1861: Louis Pasteur
- disproved spontaneous generation, which
eventually led to:
(a) development of sterilization
(b) development of aseptic
techniques

Louis Pasteur
(1822-1895)

Department of Chemical Engineering

University of San Carlos

Fermentation is
degradation of organic substrates
(by microorganisms) in
conditions where oxygen is
absent!
16

Brief history: significant contributions

Robert Koch
(1843-1910)

1882: Robert Koch

Kochs postulates
provided
guidelines to
identify the
causative agent
of an infectious
disease.
Department of Chemical Engineering
University of San Carlos

17

Brief history: significant contributions

1882: Robert Koch
Kochs postulates: the critical test
for the involvement of a
microorganism in a disease
leading to:
development of pure culture
techniques
stains, agar, culture media,
petri dishes

Department of Chemical Engineering

University of San Carlos

18

Discovery of causative agents of microbial diseases

Date

Disease/infection

Causative agent

Discoverer

1876
1879
1880
1881
1882
1882
1883
1883/84
1884
1885
1885
1886
1887
1887
1888

Anthrax
Gonorrhea
Typhoid fever
Wound infections
Tuberculosis
Glanders
Cholera
Diphtheria
Swine erysipelas
Tetanus
Bacterial pneumonia
Meningitis
Malta fever
Equine strangles
Chancroid

Bacillus anthracis
Koch
Neisseria gonorrhea
Neisser
Salmonella typhi
Eberth
Staphylococcus aureus
Ogston
Mycobacterium tuberculosis
Koch
Pseudomonas mallei
Loeffler & Schutz
Vibrio cholerae
Koch
Corynebacterium diphtheriae Klebs/Loeffler
Erysipelothrix rhusiophathiae
Loeffler
Clostridium tetani
Nicolaier
Streptococcus pneumoniae
Fraenkel
Neisseria meningitidis
Weichselbaum
Brucella spp.
Bruce
Streptococcus spp.
Schutz
Hemophilus ducreyi
Ducrey
19

Department of Chemical Engineering

University of San Carlos

Discovery of causative agents of microbial diseases

Date
1892
1894
1895
1896
1897
1898
1898
1905
1906
1909
1912

Disease/infection

Causative agent

Discoverer

Gas gangrene
Clostridium perfringens
Welch & Nuttall
Plague
Yersinia pestis
Kitasato & Yersin
Fowl typhoid
Salmonella gallinarum
Moore
Botulism (food poisoning) Clostridium botulinum
Van Ermengem
Bangs disease
Brucella abortus
Bang
(bovine abortion)
Dysentery
Shingella dysenteriae
Shiga
Pleuropneumonia of cattle Mycoplasma mycoides Nocard & Roux
Syphilis
Treponema pallidum
Schaudin & Hoffmann
Whooping cough
Bordetella pertussis
Bordet & Gengou
Rocky mountain spotted fever Rickettsia ricketsii
Ricketts
Tularemia
Francisella tularensis
McCoy & Chapin

Department of Chemical Engineering

University of San Carlos

20

10

Brief history: significant contributions

1901: Martinus Beijerinck
- formulated the concept of
enrichment culture, a selection
of specific microorganisms from
a natural sample using
specific culture media and
incubation conditions

Department of Chemical Engineering

University of San Carlos

Martinus Willem Beijerinck

(1851-1931)

21

Brief history: significant contributions

1928: Alexander Fleming
Discovered antibacterial Penicillin
from Penicillium notatum
WWII resurrected the interest in
antibiotics and some commodity
chemicals by fermentation

Chance favored the prepared mind.

Department of Chemical Engineering
University of San Carlos

Alexander Fleming
(1881-1955)
22

11

General Introduction
Industrial Microbiology

Protists

ushered in by the requirements

of war (Penicillin story)
production of acetone, butanol,
glycerol, etc from pure cultures
availability of antibiotics and
other wonder drugs
ancient history of preserving
food and preparing beverages
using microorganisms

23

Department of Chemical Engineering

University of San Carlos

General Introduction
Biochemical Engineering
In the 1940s, developments in biochemistry,
microbial genetics and engineering ushered
the era of antibiotics which marked the birth
of biochemical engineering, the engineering
of processes using catalysts, feedstocks
and/or sorbents of biological origin.

Department of Chemical Engineering

University of San Carlos

24

12

General Introduction
Challenge of multi-disciplinary approaches
management of microbial growth
processes
understanding and controlling of
factors for microbial growth
genetic manipulation: mutation and
screening
optimising media and growth
conditions
process control of microbial growth
and product formation
process and product development
new processes and new products
25

Department of Chemical Engineering

University of San Carlos

Integration of Disciplines
Biochemistry Microbiology
Genetics
Microbial Physiology

Molecular biology

Process Technology & Engineering

Bioconversion

Fine/heavy
chemicals

Food & Pharmaceuticals

Agriculture
beverages

Department of Chemical Engineering

University of San Carlos

Waste
Purification

Fuels &
energy
26

13

27

Department of Chemical Engineering

University of San Carlos

Biological Processes
..processes that use living cells or components of
such cells for the production of useful substances;
catalysts involved are biocatalysts such as
enzymes or the microorganism itself.

Department of Chemical Engineering

University of San Carlos

28

14

Micro-organism: the heart of fermentation

Diversity of nature!
29

Department of Chemical Engineering

University of San Carlos

Fermentation
RECALL: 1880s Louis Pasteur
...degradation of organic substrates (by
microorganisms) in conditions where oxygen is
absent!
Traditionally,
it is the application of the production of potable alcohol from
carbohydrates;
process for the production of alcohol or lactic acid from glucose.
C6H12O6 2 C2H5OH + 2 CO2 by yeast as catalyst
C6H12O6 2 CH3CHOHCOOH by enzymes as catalyst
Department of Chemical Engineering
University of San Carlos

30

15

Fermentation
Nowadays,
it is also the enzymatically
controlled transformation of an organic
compound.
Workhorse
biocatalyst
microorganisms

fermenter bioreactor
Department of Chemical Engineering
University of San Carlos

fermentation biotransformation

31

Touching base: history

Louis Pasteur
Father of Biochemical Engineering
Microbes produced from preexisting living matter
Microbes can exist in the absence
of O2
Different products with change in
conditions
Attenuated microbes gave the
body immunity

Department of Chemical Engineering

University of San Carlos

32

16