CHE 172

COURSE OVERVIEW AND CLASS POLICIES

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Course Description
Introduction to Biochemical Engineering
OBJECTIVES OF THE COURSE
Provide concepts in microbiology and biochemistry relevant to bioprocessing introduction to the mathematical aspects of cell growth and application to bioreactor design introduction to chemical engineering aspects of industrial sterilization and bioseparation (downstream processing) technologies

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Course Requirements
4 Long Exams SARQ (Seatwork, Assignment, Recitation, Quizzes) Oral/Written Report on the Industrial Production of a Biotechnological Product (if there is still time)
PREFINAL GRADE= Average of LE + SARQ + (Report)

FINAL GRADE= 70% PreF Grade + 30% Final Exam

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Course Requirements (contd)

Exemption from Final Exams:

A PreFinal Grade of 70% with No Long Exam grade lower than 50%

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CHE 172 Lecture A

Introduction to Biochemical Engineering and Industrial Bioprocessing
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BIOTECHNOLOGY
the practical application of biological agents
(living/dead cells or the sub-cellular components)

in technically useful operations ,

either in productive manufacture, services operations or environmental management

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Biological Agents
Microorganisms (Bacteria, Yeasts, Filamentous Fungi, etc) Plant/Animal Cells Sub-cellular components, Enzymes

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Technically Useful Operations

Manufacture of an economically useful/value added product
Single cell protein, pharmaceuticals, industrial chemicals, etc

Waste Treatment/Biodegradation/Bioremediation

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BIOTECHNOLOGY IS A BIG INDUSTRY (variety of products)

Fermentation Product Typical organism used Approximate World Market (tons/yr) 2 x 107 2 x 106 0.5-1 x 106

Bulk organics Ethanol Acetone/butanol

Biomass Single-cell protein Organic acids Citric Acid Lactic Acid Amino acids L-glutamate L-lysine L-phenylalanine

Saccharomyces cerevisiae Clostridium acetobutylicum Candida utilis/ Pseudomonas, methlotrophus, Bakers yeast

Aspergillus niger Lactobacillus delbrueckii

Corynebacterium glutamicum Brevibacterium flavum Corynebacterium glutamicum

2-3 x 106 2 x 105

3 x 106 3 x 105 2 x 103

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BIOTECHNOLOGY IS A BIG INDUSTRY (variety of products)

Fermentation Product Exocellular polysaccharides xanthan gum dextran Enzymes proteases amylases pectinases Vitamins Vitamin B12 Pigments shikonin beta-carotene Typical organism used Approximate World Market (tons/yr)

Xanthomonas campestris Leuconostoc mesenteroides Bacillus sp. Bacillus amyloliquifaciens Aspergillus niger Propionicum shermanii Lithospermum erythrohizon (plant cell) Blakeslea trispora

5 x 103 small 6 x 102 4 x 103 10 10 60 kg/yr

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BIOTECHNOLOGY IS A BIG INDUSTRY (variety of products)

Fermentation Product Typical organism used Approximate World Market (tons/yr)
< 50 kg/yr

Vaccines tetanus hepatitis B

Therapeutic proteins Insulin Interferon Monoclonal antibodies

Clostridium tetani Surface antigen in recombinant yeast Recombinant E. coli Recombinant E. coli hybridoma cells

< 20 kg/yr < 20 kg/yr

Antibiotics penicillins cepaholosporins tetracyclines

Penicillum chrysogenum Cephalosporium acremonium Streptomyces aureofaciens

3-4 x 105 1 x 105 1 x 105 A-11

Biotechnology:
An Interdisciplicary Endeavor

The ability to harness capabilites of cells (development of new products and processes) usually starts in the laboratory: Microbiology, Biochemistry , Cell physiology, Molecular biology/Genetics

Bringing a bioprocess to industrial realization requires engineering skills and know-how: Biochemical engineering or Bioprocess Engineering
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What is the importance of biochemical engineering in the biotechnology industry?

Biochemical engineering is one of the major areas of biotechnology important to its commercialization (Lee 1992).
Successful commercialization of biotechnology requires the development of a technologically viable and economically efficient process.
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Role of the biochemical engineer for commercial realization of biotechnology

(1)Bioreactor: scale up, design, optimal operation and control (2)Downstream processing equipment: design and operation (3)Fermentation plant design

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ORIGINS AND EVOLUTION OF BIOTECHNOLOGY

How did industrial fermentations begin?

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EVOLUTION OF BIOTECHNOLOGY The First Wave

Microbial Production of Food and Beverages
6000 BC Sumerians and Babylonians were already drinking beer (accidental observation?) 4000 BC Egyptians were already baking leavened bread wine was known in the Near East by the time of the Book of Genesis
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EVOLUTION OF BIOTECHNOLOGY The First Wave

Microbial Production of Food and Beverages
More of a craft;

involvement of microbes not yet known

Microbial Production of Food and Beverages

By 17th Century, the realization that microorganisms had a role in wine, beer making started Anton van Leeuwenhoeks microscope
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EVOLUTION OF BIOTECHNOLOGY The First Wave

Microbial Production of Food and Beverages
Louis Pasteur gave definitive proof of the the fermentative abilities of microorganisms Louis Pasteur can justifiably be considered as the father of biotechnology

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EVOLUTION OF BIOTECHNOLOGY The First Wave

Microbial Production of Food and Beverages
Other Microbially bases processes: fermented milk, yoghurt, cheeses, soy sauce, tempeh, etc.

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EVOLUTION OF BIOTECHNOLOGY The Second Wave

Biotechnological processes initially developed under non-sterile conditions

many industrial compounds such as ethanol, acetic acid, organic acids, butanol and acetone were produced by the end of the 19th century by microbial fermentation procedures that were open to the environment the control of contaminating microorganisms were achieved by careful manipulation of the ecological environment and not by complicated engineering practices. municipal composting of solid wastes and wastewater treatment are outstanding examples of non-sterile biotechnology

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EVOLUTION OF BIOTECHNOLOGY The Third Wave

The introduction of sterility to biotechnological processes A 1940s: a new direction in biotechnology with the introduction of complicated engineering techniques to the mass cultivation of microorganisms to ensure that the particular biological process could proceed at higher yields with the exclusion of contaminating microorganisms. (birth of biochemical engineering thought to be here) period of increasing volumes of biotechnological activies: antibiotics, amino acids, organic acids, enzymes, steroids, polysaccharides, vaccines
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Modern Bioreactor
http://www.biotopics.co.uk/edexcel/fermtr.gif

EVOLUTION OF BIOTECHNOLOGY The Third Wave

The introduction of sterility to biotechnological processes
A 1940s: a new direction in biotechnology with the introduction of complicated engineering techniques to the mass cultivation of microorganisms to ensure that the particular biological process could proceed at higher yields with the exclusion of contaminating microorganisms. (birth of biochemical engineering thought to be here) period of increasing volumes of biotechnological activies: antibiotics, amino acids, organic acids, enzymes, steroids, polysaccharides, vaccines

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EVOLUTION OF BIOTECHNOLOGY The Fourth Wave

Explosive developments in molecular biology and process control have created new and exciting opportunities to create new frontiers and to improve greatly the efficiency and economics of the established biotechnological industries production of human insulin from E. coli, monoclonal antibodies for detection and treatment of diseases plant tissue/animal cell culture protoplast fusion artificial intelligence for control of bioreactors artificial organs, stem cells

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STEM CELL TECHNOLOGY

Stem cells are the source, or stem, for all of the specialized cells that form our organs and tissues. Thats why stem cells are able to change into other types of cells, something no other kind of cell can do.

Each time a stem cell divides, it can remain a stem cell or change into a heart, blood, brain, or other type of cell.
Theoretically, stem cells can even divide without limit to replenish themselves and other cells.

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Stem cells are found in very early embryos and a few adult organs. In embryos, stem cells produce the first cells of the heart, brain, and other organs.
In adults, stem cells can be found in a few kinds of tissues that need constant replenishing. For example, stem cells in bone marrow produce new blood cells to replace those lost through normal wear and tear or injury. An important difference between embryonic and adult stem cells involves how many different types of cells they can develop into. Embryonic stem cells have the potential to form just about any kind of cell in the body, but Adult stem cells are only able to form a few new cell types.
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THE BIRTH OF BIOCHEMICAL ENGINEERING

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The Birth of Biochemical Engineering

Necessity to produce large quantities of more effective antimicrobials for the war effort (WW II) Many soldiers dying from infectious wounds Sulfa drugs losing effectivity due to resistance

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The Birth of Biochemical Engineering

Scientists at Oxford University rediscovers Alexander Flemmings earlier publication on the germicidal properties of mold juice which was largely unnoticed Germicidal component named Penicillin, after the genus of the mold Oxford University scientists proved that penicillin could effectively treat wound infections

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The Birth of Biochemical Engineering

Penicillin was heralded as a wonder drug at the time Intial attempts for mass production was space consuming with very low product yields (as low as 0.001 g/L) Pfizer was the first pharmaceutical company to take the challenge of mass producing penicillin After 3 years of difficulty (low yield and stability of product), and new approach using deep tank fermentation (submerged fermentation) was attempted.
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The Birth of Biochemical Engineering

The chemical engineering techiques learned for high penicillin production by fermentation in a stirred tank reactor became the foundation for the biochemical engineering field The penicillin yield increased 50-fold

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The Birth of Biochemical Engineering

The penicillin process also established a paradigm for bioprocess development and biochemical engineering. This paradigm still guides much of the professions thinking. The mind set of bioprocess engineers was cast with the penicillin experience.

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Commercialization of Biotechnology Involves Scale Up from Laboratory Scale (small) to Production Scale (large)

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Small Scale vs Large Scale

How Does the Story Change?

SMALL SCALE LARGE SCALE

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Small Scale vs Large Scale

How does the story change when you implement the following stages of fermentation from small to large scale? (1) (2) (3) (4) (5) Medium preparation Sterilization Inoculation Main Fermentation Product Separation and Purification (downstream processing)
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