Problems and Opportunities
in the Viola Section
SWEA Assembly 2014
Wednesday, 11 June 2014
Sarnia, ON
David Dodds, Dodds & Associates
DODDS & ASSOCIATES © 2014
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DA
Axioms
(and qualifications)
Corn ethanol is a fabulous success story.
But there is more than corn, and more than fuel.
If you are making a molecule,
you are a chemist, doing chemistry.
Synthetic biology is just chemistry conducted by other means.
“Bio” does not change the molecule.
Redox Balance
It’s not the carbon, it’s the hydrogen.
DODDS & ASSOCIATES © 2014
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Why?
Markets want alternative to petrochemical feedstock
• de-linking commodity chemical production from oil prices
• Hedge against carbon taxes
• Availability of feedstock from multiple locations;
not just price, but supply-chain security
Technical hurdles dropping
• Molecular biology, biocatalysis, fermentation technology,
petrochemical processes & engineering
Opportunity to use under-utilized assets and existing infrastructure
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Some History
1833: diastase (amylase) isolated from barley, shown to convert starch to sugar
1860: Pasteur showed yeast transforms sugar to alcohol and butanol (1861)
1860s: vitalistic and non-vitalistic theories of organized and un-organized "ferments”
(Pasteur, Liebig, and Berzelius)
1876: Kühne coined term "enzyme" ("in yeast") for organized ferments
1881: Frémy and beginning of industrial production of lactic acid
1898: last vitalistic paper; F.R. Japp, Nature, 58, 482 (1898)
1905: biological production of acetone discovered by Shardinger
1912: Fernbach patents acetone and butanol production
1916: Immobilized invertase used industrially
1919: Weizmann patents acetone and butanol production (GB4845, US1315585)
1950: 2/3 of all US butanol (~30 MM lbs), 50% of ethanol (~225 MM gal) and
10% of acetone made from molasses & starch
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We Have Done This Before
H. Bunn, Industrial and
Engineering Chemistry,
44(9), 2128 1952
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2013 Numbers (US)
Product
Gasoline
Heating Oil/Diesel Fuel
Jet Fuel (Kerosene)
Propane/Pr opylene
NGL, Liquid Refinery Gases
Still Gas
Pe troche m icalFeedstock s
Petroleum Coke
Residual/Heavy Fuel Oil
Asphalt and Road Oi
Lubricants
Miscellaneous Products
Other Liquids
Aviation Gasoline
Special Naphthas
Waxes
Kerosene
% of Total US Oil
Consumption
47%
20%
8%
6%
6%
4%
2%
2%
2%
2%
1%
0.4%
0.4%
0.1%
0.04%
0.04%
0.02%
EIA November 2013
www.eia.gov/dnav/pet/pet_sum_snd_d_nus
_mbbl_m_cur.htm
75% vs 2%
In 2005, ratio was 71% vs 3.5%, with economic impact of $365BB vs $375BB
In 2013 had dropped to $255BB
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Making, and buying, less….
….losing integration and value
www.eia.gov/dnav/pet/hist
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Chemical Feedstock:
(just corn, just glucose)
US 2013 corn production; 13.8 BB bushels = 350 MM tonnes
1 tonne corn = 590 kgs glucose (C6H12O6)
= 275 kgs “CH2 equivalent”
= 2 bbl oil (1 bbl oil = 139 kgs)
So current corn production on a simple “CH2” weight basis = 700 MM bbl oil
US oil consumption (2012) = 18.5 MM bbl/day = 6.75 BB bbl/yr
2% of oil consumed is for chemical feedstocks = 0.135 BB bbl/yr
•
On a simple weight basis, ~20% of current US corn crop could
theoretically satisfy US chemical feedstock production
Currently, ~42% of current US corn crop goes to EtOH
Estimated that the entire 1.3 BB tons annual renewable biomass would
replace about half of the US transportation fuel
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Problems
Lack of Champion for Chemicals
• US DoE has energy mandate, which includes fuels
• USDA has biomass mandate - for eating, building, burning, etc.
Lack of Standards
• ASTM D6866 is fine, but not enough
• What is “renewable”? “sequestered”? “bio-based”?
Lack of Policy
• US federal planning is minimal at best
• RFS/RINS, TSCA, R&D tax credits
Lack of Funding
• The über problem (a product of taxation, R&D tax credit uncertainty, etc.)
• Cost-sharing, incubators, consortia; these all cost money….
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The über Problem
• 30 start-ups in the $BB Valuation Club; 1 bioenergy (#17), 1 solar (#29)
• Trends in investment are short, fashionable, and risk-adverse
• Money from the private sector (corporations) is very hard to attract
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Operational Opportunities
Advocacy
• A champion for bio-based chemicals; an advocacy group
• Need to address lack of policy by direct lobbying/politics
New Paradigm for IP
• Just equity for the licence fee
• Royalties possible, but not until full commercial production; no minimums
Incubators
• Additional overhead for start-up is a non-starter today
• Equity, with rent payments beginning and ramping up after 24 months
Grants (US)
• SBIR funding is great, but is US-only, and there is not enough
• Other FOAs allow foreign entities
• A vehicle for cost-sharing and the non-technical parts of the grant package
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Technical Opportunities
“Lignin”
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Lignin and Hemi-cellulose
Hemi-cellulose
• 15% (or more) of tree mass is recoverable
• Extracted with hot water and easily depolymerized to 5-carbon sugars
• Commercially valuable by-products; acetic acid, methanol, etc.
Lignin
• ~20% of all biomass
• 1.3 BB tonnes renewable biomass each year in US
= 260 MM tonnes lignin
• US consumption of BTX, phenol, PTA is ~30MM tonnes
• 10% efficiency across collection & conversion = ~300 MM tonnes
• at 10% efficiency, we are just short of total replacement
of the feedstock need for major aromatic chemicals
• Phenylpropionic monomers hard to reach
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Lignin Biochemistry
24-25 steps; ~70% average carbon efficiency
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What is the value of this molecule?
(ask your chemists)
R1 , R2 , R3 = H, OH, OCH3
R4 = COOR, CH2OH
Decarboxylation to styrenes
Ring-opening with dioxygenases
Not just woody biomass!
Corn fiber contains 2-3% ferulic acid
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Hemi-cellulose:
(not glucose, not fermentation)
Just four chemical processes applied to C5 monomers
All amenable to continuous petrochemical process design
….but we need some hydrogen
www.prnghrn.com; PCT/US/14/027269
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Redox & Hydrogen
We generally want to make molecules more reduced than carbohydrates,
which occupy the center of the redox range of carbon
Biological pathways can use H2 gas, but other forms of reducing equivalents
are far more common; NADH, NADPH, FMNH2 etc. and this is generated by
oxidizing carbohydrate feedstock to CO2
This costs carbon! If we make hydrogen, we lose carbon.
3 O2 + C6H12O6  6 H2 + 6 CO2
1 mt H2 costs;
• Carbohydrate at $400/mt
• Electricity at $60/MW
• Methane steam cracker
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


$6000
$3200
~$1800
&
DA
Why is Hydrogen Important?
Ethanol
(50%)
1 glucose  2 EtOH + 2 CO2
9 H2 + 1 glucose  3 EtOH
Butanol
(50%)
1 glucose  1 BuOH + H2O + 2 CO2
6 H2 + 1 glucose  1.5 BuOH + 4.5 H2O
1,4-BDO
(100%)
11/12 glucose  1 BDO
10 H2 + 2 CO2 + 1 glucose  2 BDO
+ 0.5 H2O + 1.5 CO2
+ 6 H2O
Difficult to handle H2 gas in a fermentor; hazardous and gas/liquid transfer
Electrochemical methods to add reducing equivalents avoids this, and
allows “hydrogen distribution” via existing electrical grid
WO2014/039767 and earlier work at MSU
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Biocatalysis: An Overlooked Technology
The use of biological catalysts - enzymes - as isolated catalysts under nonphysiological conditions
The last 25 years have seen there increasing use in pharma especially
Rapid advances in relevant biological platform technologies
Almost completely unused in chemical industry, yet can be used in
standard industrial catalytic process configurations
These catalysts are just high molecular weight polyamides that do not
contain precious metals…
…and are getting much easier to make!
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Extremely Rapid Technology Growth
Publications
Cost of Sequencing
Published Protein Structures
Many public databases with
complete pathways
www.genome.jp/kegg
www.brenda-enzymes.info
www.ncbi.nlm.nih.gov/genome
www.yeastgenome.org
Number
100k
10k
1990
DODDS & ASSOCIATES © 2014
2012
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Pharma Chemical Reactions:
Biocatalysis Contribution
16
14
12
10
8
6
4
2
0
• Pharma has been busy building the technology base for ~25 years
• Activities available in 2 weeks to 2 months; industrially relevant timing
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Biocatalysis Applications
Immobilized Cells for Continuous Processes
• Catalyst containment and stability; avoids isolation & purification issues
• Multiple reactions possible (metabolic pathways intact, including redox)
Cell-free Process Configurations
 Protein engineering is available, practical and timely
 Use packed-bed reactors; same as petrochemical industry
 Easily scaled, stability needs to be in 6-month range
 Spatial separation of multiple enzyme steps
Redox Chemistry
 Remains important and still difficult for chemists
 Electrochemical regeneration of cofactors
DODDS & ASSOCIATES © 2014
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Our Opportunities
• Advocacy: a champion for bio-based chemicals policy
Do what the small company cannot; actions where organizational
size and membership numbers really do matter
• IP: New Paradigm for moving from academia to start-ups
• Reconsideration of Incubators and their operation
• A vehicle for handling the non-technical aspects of grants
This has enormous value but is boring - and difficult.
• A practical and unified message from our community
We are distracted by biofuels. We need fixed policy.
We need funds that actually reach the bench rather than
supporting other organizational infrastructures.
DODDS & ASSOCIATES © 2014
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DA
David R. Dodds, Ph.D.
Dodds & Associates LLC
MOBILE 315 884 3703 / TWITTER drdodds4
ddodds@techdiligence.net
www.techdiligence.net
www.linkedin.com/in/techdiligence
DODDS & ASSOCIATES © 2014
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DA