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Bioprocess Engineering and Renewable
Energy
Maobing Tu
Chemical and Environmental Engineering
University of Cincinnati
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Running and energy
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The 4th revolution
• https://www.youtube.com/watch?v=unaY8mgo2S0
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Four industrial revolutions
Technologies that combine physical, biological and digital worlds
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Energy?
 What is energy?
 Where does the energy coming from?
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Energy resource
• https://www.youtube.com/watch?v=qjnm3V0xYjI
• Every star is powered by a process known as "fusion," in which atoms
fuse together while some of their mass is converted to energy.
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Fusion energy and Fission energy
• Famous equation E=MC2
• One gram (mass) equals 85.2 billions BTus
1 amu=1.66x10-27 kg
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Energy literacy
• Energy: the ability of a system to do work
• Work: work equals force times distance
• Power: a measure of energy transfer rate
www.grc.nasa.gov
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Energy literacy
• Energy is neither created nor destroyed (First law)
• Energy Forms:
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Heat (thermal) energy
Light (radiant) energy
Motion (kinetic) energy
Electrical energy
Chemical energy
Nuclear energy
Gravitational energy
• Energy Type
• Potential Energy
• Kinetic energy
• http://www.pbslearningmedia.org/resource/hew06.sci.phys.maf.rollercoaste
r/energy-in-a-roller-coaster-ride/
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U.S. history of energy consumption
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How to measure energy
• Different units
• Joules
• Calories
• Kilowatt-hours
• Btu (British thermal Unit)
• Relationship
• 1Btu=1,000 joules
• 1 Calorie=4.186 joules
• 1 KWh=3.6x106 Joules
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U.S. energy consumption
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Renewable Energy
• Solar energy from the sun
• Wind energy from wind for practical purposes
• Hydro energy from hydroelectric turbines
• Geothermal energy from the heat inside of the earth
• Biomass from plants and crops, wood chips, corn ethanol, biodiesel
from vegetable oil
http://technologygreenenergy-e-online.blogspot.com
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Solar energy
Advantages
Disadvantages
Completely renewable
Solar cells and solar panels very
expensive
No air, water, or noise pollution
Light/Weather dependent
No greenhouse gases emission`
Low efficiency (20% sun rays to
electricity)
Low operating cost
Large areas of land
Used in remote areas
Photovoltaic panel made of silicon
and toxic metals (mercury)
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Wind energy
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Biofuels and bioenergy
Nature 454, 841 (2008)
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New course on renewable energy
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Bioenergy and biofuels-Europe point of view
• http://www.youtube.com/watch?v=xL_fVnKYjrg
• From Europe point of view
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Catalyst and biocatalyst
Zeolite
Yeast
Enzyme
www.catalysisbook.org
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Catalyst and chemical/environmental
engineering
• Chemical/environmental engineers turn molecules into money
• develop and operate processes to convert raw materials into valuable
products
• Reactor design, process control, reaction kinetics, mass and heat transfer and
separation
• Catalyst plays essential role in many of these processes
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Biocatalyst and chemical engineering
• UCLA-ChemE (James Liao)
• Metabolic engineering & synthetic biology
• Isobutanol-producing biocatalyst
• UC Berkely-ChemE (Jay Keasling)
• Biochemical engineering & metabolic engineering
• Hydrocarbons-producing E. coli and S. cerevisiae
• Catalysis & reaction engineering
• “The challenge in designing the catalyst is to increase its effectiveness and
stability”
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Our research: fuels and chemicals
Ethanol
Lactic acid
butanol
Gluconic acid
Butyric acid
Acrylic acid
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Our research on acrylic acid
• Integrating biochemical conversion and chemical catalysis to produce
new chemicals
• Biomass to lactic acid by fermentation
• Catalytic conversion of lactic acid to acrylic acid
Procter & Gamble
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Our research on butanol
• Biofuels and bioproducts manufacturing
• Butanol production from renewable biomass by Clostridium acetobutylicum
• Robust biocatalyst (strain) development
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Drivers-why biofuels and bioenergy
• Increase energy security and reduce the nation’s
dependence on foreign oil
• Reduce greenhouse gas (GHG) emission
• Enhance sustainability of liquid fuels
• Create new economic opportunities and jobs
• Utilize 1 billon tons of renewable biomass (U.S.)
http://www.nrel.gov/biomass/biorefinery.html
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U.S. oil consumption and production
• U.S. oil consumption 18.9 million barrels per day
• U.S. oil production 12.3 million barrels per day
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U.S. oil consumption and production
• U.S. spending $427 billion on imports in 2013
• Facing critical disruptions in oil supply
• Influencing national security
http://time.com/67163/why-are-u-s-oil-imports-falling/
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U.S. CO2 emission
http://edgar.jrc.ec.europa.eu
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Why lignocellulosic biomass?
• Biomass is carbon-based organic material, including forest
residues/waste, agricultural residues, energy crops (switchgrass) and
algae
• Biomass clean renewable source of energy
• Biomass absorbs carbon during growth
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Federal initiative on bioenergy
• President Bush-2007
• “Twenty-in-Ten” initiative, reduce gasoline 20% in 10 y
• Energy Independence & Security Act mandates 36 b gallons of renewable
fuels by 2022
• Bioenergy Research Centers
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Federal initiative on bioenergy
• President Obama-2013
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$2-Billion Plan to Get U.S. Cars off Gasoline
Energy security trust (over 10 yrs.)
Natural gas fuel
Advanced batteries for electric vehicles
Cleaner biofuels
Hydrogen fuel
http://blogs.scientificamerican.com/observations/2013/03/
15/obama-to-announce-2-billion-plan-to-get-u-s-cars-offgasoline/
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Bioenergy research centers
DOE Joint BioEnergy Institute
DOE Great Lakes Bioenergy Research Center
DOE BioEnergy Science Center
• Receive $25 million per year (4/4/13)
• Innovative biofuel research for another fiver years
BP Energy Biosciences Institute
• UC Berkeley and Univ. of Illinois at Urbana-Champaign
• $500 million, 10-year award (2007)
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DOE Bioenergy research centers ($375M)
• Joint Bioenergy Institute (Jbei, Jay Keasling)
• DOE’s Lawrence Berkeley National Laboratory and Sandia National Laboratories
• DOE’s Lawrence Livermore National Laboratory
• UC Berkeley; UC Davis; Stanford University
• BioEnergy Science Center (Paul Gilna)
• National Laboratory in Oak Ridge and National Renewable Energy Laboratory
• Georgia Institute of Technology
• University of Georgia; Dartmouth College and UC Riverside
• Great Lakes Bioenergy Research Center (Timothy Donohue)
• University of Wisconsin in Madison, Wisconsin
• Michigan State University; DOE’s Pacific Northwest National Laboratory
• University of Florida; DOE’s Oak Ridge National Laboratory
• Illinois State University and Iowa State University
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Using microbes to manufacture biofuels
• https://www.youtube.com/watch?v=fLcYrXSGFZg
• Jay Keasling
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Integrated biorefinery
Integrated Biorefinery Projects Funded by DOE
http://www1.eere.energy.gov/biomass/pdfs/ibr_portfolio_overview.pdf
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Integrated biorefinery projects funded (DOE)
 INEOS first commercial biorefinery (8MG)
 POET-DSM & Abengoa produce ethanol (20/25MG)
 Myriant produces biobased succinic acid (30 MP)
http://www1.eere.energy.gov/bioenergy/pdfs/replacing_barrel_overview.pdf
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Biorefinery pathways
• Thermochemical conversion (gasification/pyrolysis)
• Biochemical conversion (enzymes/microbes)
https://www1.eere.energy.gov/bioenergy
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National Renewable Energy Lab
 Biochemical conversion to biofuels
 https://www.youtube.com/watch?v=wz6rdco_v7k
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Glucose to ethanol yield
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Department of Energy-themochemical
conversion
• https://www.youtube.com/watch?v=kI7s6IRpOHA
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Stirling engine
• Heat engine with gaseous working fluid
• Conversion of heat energy to mechanical work
• Used in submarines
• Gasses never leave the engine
• No exhaust valves and no explosions, quite
• Stirling cycle from external heat source
• Operate by cyclic compression and expansion of air
• by a temperature difference in the engine
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Glucose to ethanol
http://www.nature.com/scitable/resource?action=showFullImageForTopic&img
Src=/scitable/content/ne0000/ne0000/ne0000/ne0000/14649661/f3_alba_ksm.
jpg
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Insulin and first biotech drug
• 1978: First successful
• 1982: The first biotech drug, human insulin produced in genetically
modified bacteria developed by Genentech and approved by Food
and Drug Administration (FDA).
• Manufactured and marketed by Eli Lilly under a license from
Genentech
• Collaboration is important
• Insulin is a protein hormone produced in pancreas
• Used in metabolism of sugar and other carbohydrates
• Treatment of diabetes (one adult in ten 10 will have diabetes by
2030)
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Diabetes, glucose and insulin
• https://www.youtube.com/watch?v=ae_jC4FDOUc
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Insulin structure
• Chain A 21 amino acids
• Chain B 30 amino acids
• 2 conserved disulfide bridges
• Can form dimers in solution
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Human insulin produced in E. coli
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Human insulin produced in E. coli
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How insulin is produced in industry
• https://www.youtube.com/watch?v=iMosKBs-v0E
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• How insulin produced in Sweden and Nova disc company
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Amgen—success story: From drug development
to mass market
• Founded in 1980 (Thousand Oaks, California)
• George Rathman (CEO), one of the great geniuses
• Invested by venture capitalist
• IPO in 1982 and raised $42.3 million
• IPO (Initial public offering) is the first sale of a company's shares to
the public, leading to a stock market listing
• Big challenge was: which products to develop (?)
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Amgen attempted various products
 Develop microbes
to extract oil from shale
 Grow chicken faster
 Make specialty chemicals (acrylic acid)
 Clone light source of luciferase
 Produced indigo dye in E. coli
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Focus and focus
 Business-minded scientist (Rathmann)
 Strict timetables and goals
 Target only one product
 Clone erythropoietin (EPO) gene for stimulating red blood cell
production
 Treat anemia resulting from chronic kidney disease
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Bio-manufacturing
Joint venture with Kirin
Commercialization of erythropoietin
1989: FDA approved Epogen (first drug)
1992: $1 billion products sales (Epogen and
Neupogen)
• 2014: Annual revenue, $20.1 billion
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Successful lessons
 Talent scientists team
 Well-managed R&D
 Strategic focus
 Successful fund raising
 Synergistic partnership
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Flint water crisis
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Yeast and bacteria
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Structure & function of bacterial cell
Ribosomes
cell protein synthesizing factories
Cell membrane
Pass in and out of chemicals
selectively
Cell wall
Structural strengthening of cell
Cytoplasm
materials/structures carry out the
functions of cell
Circular DNA
Genetic code
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Structure & function of yeast cell
Ribosomes
cell protein synthesizing factories
Cell membrane
Pass in and out of chemicals
selectively
Cell wall
Structural strengthening of cell
Cytoplasm
materials/structures carry out the
functions of cell
Nucleus
Genetic code
Mitochondria
Contains enzyme for reactions in
aerobic respiration
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Microbial cell as machine and coding device
www.studyblue.com
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Story of penicillin
• Biologists and Engineers
• Biologists are good at
• Describing things
• Explaining the fundamental mechanism
• Understanding function of organism
• Engineers are good at
• Mathematics and physics
• Developing solutions for technical and commercial application
• In 1928, Alexander Fleming in London
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Science discovery by accident
• Alexander Fleming discovered penicillin on a petri dish, which had
been accidently left open for several days!
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Penicillium and penicillin
• Contaminated with a foreign particle
• Should be thrown away
• “Failed” experiment
• Cell killing------antibacterial agent
• Common mold on bread
• Penicillin, one of the greatest advances
• Therapeutics
• Combined effects in UK and USA
• World War II
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Development of penicillin
• Initial test was very effective in UK
• Healing rates of bone infection in WWI (25%) and WWII (95%)
• To produce large amount of penicillin require a process
• Due to the war, UK asked US to develop the capacity to produce
penicillin
• Companies and government labs took up the challenge
• USDA Northern Regional Research Lab (Peoria), Merck, Pfizer, Abbott
and Squibb
• Chemical synthesis vs fermentation
• https://www.youtube.com/watch?v=36x124crRVk
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Development of penicillin
• Fermentation process
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Low production rate (productivity)
Low titer (concentration), 0.001g/l
Product recovery and purification
Grows well in surface culture
• Penicillin not stable
• Especially at low and high pH
• Develop corn steep liquor-lactose based medium
• Increase productivity 10 times
• Isolate new penicillium chrysogenum from cantaloupe
• Good for submerged fermentation (?)
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Fermentation-manufacturing process
• Grow mold on the surface of moist bran
• Difficult to control temperature, sterilization and scale up
• High yield
• Long growing cycle and lab intensive
• Penicillin Manufacturing in WWII
• Bottle plant
• Worked and implemented quickly
• https://www.youtube.com/watch?v=Y2xGFtxq56s
• Submerged fermentation process
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Engineers favor submerged process
Large volume
Oxygen supply
Heat removal
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Development of penicillin
• pH shifts and rapid liquid-liquid extraction
• 10,000 gallon was built
• Pfizer completed first plant for commercial production penicillin
• Submerged fermentation
• 14 tanks (7,000 gallon)
• Penicillin for 100,000 patients per year by WWII
• Further improvement
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The penicillin yield, 0.001g/l to 50 g/l
Microbe physiology, metabolic pathways
Penicillin structure
Mutation
Process control and reactor design
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Development of penicillin
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Penicillin structure
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Penicillin
• With the development of modern antibiotics
• The concept of bioprocess engineer was born
• Nobel prize for Alexander Fleming, Ernst Boris Chian
and Howard Walter Florey in 1945
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Fermentor
• Impeller/motor
• Cooling jacket (new way?)
• Steam
• Air
• Sparger
• pH controller
• Culture broth
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