millennium talks 18.5.2017 frances arnold
TRANSCRIPT
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Innovationbyevolution:Bringingnewchemistrytolife
Frances H. Arnold California Institute of Technology
May 18, 2017
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Imag
es c
ourte
sy o
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tters
tock
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Fe
O
SCys
+�
Fe
C
SCys
RR
Fe
N
SCys
R
Carbenetransfer
Nitrenetransfer
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X
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AATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATDACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCCGCGCGACATAAGGAGTCCTCGTTTCGAGATACGTACGGCATGGTGACACCAGTTGCCCTCTGATTCCCGGAGCCTCTTTGAAAACGTCGAGTCGAATCGAAGTTCGAACCCCGGATCGGGTCCACCAACTTAGAGATGTGTGTGCGCTGACTCAGTCATTTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCAATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGT
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AATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATDACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCCGCGCGACATAAGGAGTCCTCGTTTCGAGATACGTACGGCATGGTGACACCAGTTGCCCTCTGATTCCCGGAGCCTCTTTGAAAACGTCGAGTCGAATCGAAGTTCGAACCCCGGATCGGGTCCACCAACTTAGAGATGTGTGTGCGCTGACTCAGTCATTTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCAATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGT
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MTIKEMPQPKTFGELKNL...KETSPIPQPKTFGPLGNL...KQASAIPQPKTYGPLKNL...WRRRGIPGPLGYPLVGSF...WIRKGVKGPRGLPFLGVI...FIRKGIKGPRGFPGIGML...WIRKGVKGPRGFPFFGVI...WIRKGVKGPRGFPFFGVI...WMRKGIKGPRGLPFFGII...WMRKGVKGPRGRPFVGVL...WRRRGVVGPMGFPVLGVF...REKIGLSGPEPHWFLGNL...REKIGLTGPEPHWFMGNL...RSSIGIPGPPVHWLWGNL...KVSKYPKGPLPLPFIGNI......
Enzyme families are the products of millions of years of mutation and natural selection.
mutationandselection
Ancestralenzyme
Evolution does it very well.
Each molecule is well adapted to its biological role.
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Nature does it in real time: atrazine
• 1950–1993 non-biodegradable; accumulated in soil• From 1993 onwards, fast degradation observed
N
N
N
Cl
NH
NH
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the internetofliving things
Crowd-sourcing problem solving for 3+ billion years
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Humans have altered the biological world using evolution by artificial selection
for thousands of years.
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Natural mechanisms for generating sequence diversity are limited
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Not so in the test tube…
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Sex (DNA recombination) is effective strategy for creating new sequences and functions.
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MTIKEMPQPKTFGELKNL...KETSPIPQPKTFGPLGNL...KQASAIPQPKTYGPLKNL...WRRRGIPGPLGYPLVGSF...WIRKGVKGPRGLPFLGVI...FIRKGIKGPRGFPGIGML...WIRKGVKGPRGFPFFGVI...WIRKGVKGPRGFPFFGVI...WMRKGIKGPRGLPFFGII...WMRKGVKGPRGRPFVGVL...WRRRGVVGPMGFPVLGVF...REKIGLSGPEPHWFLGNL...REKIGLTGPEPHWFMGNL...RSSIGIPGPPVHWLWGNL...KVSKYPKGPLPLPFIGNI......
Sex with molecules
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Performance
0
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0 1 2 3 4 5 6 7
Gen1 2 3 4 5
Directed evolution (iterative mutation and artificial selection) can re-optimize biological molecules for new functions.
Evolved protein doing a new job
Native protein doing its native job
Native protein doing a new job
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Second most abundant element in the Earth’s crust
Si14
28.0855Silicon
...the literature is void of examples of biologically synthesized, either in vivo or in vitro,
silicon-carbon bonds.Silicon 2009, 1, 147.
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NH
SiOHR
R
catalysts / ligands
SiR3reagents for cross-coupling
Si
18F-acceptors for PET imaging
Si(i-Pr)3
Si(i-Pr)3materials for organic LED
biological probes and drug leads
O
NH
H2N
Me3Si O
OH
18FRR
3
Human chemists make lots of things with silicon-carbon bonds
lubricants, sealants, coatings…
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Rhodothermus marinus cytochrome c
Si H
MeMeN2
Me
O
OEtMe
O
OEtSiMeMeRma cyt c
+
• Made by a gram-negative, thermohalophilic bacterium• small protein – 124 amino acids• Tm = 106 °C
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Directed evolution converted this protein into a highly active catalyst for silicon-carbon bond formation…
0
500
1000
1500
2000
WT M100D V75TM100D
V75TM100DM103E
TTN
97%ee
>99%ee
>99%ee
>99%ee
(act
ivity
)
...inside living cells.
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70+ employees at Gevo Headquarters in Englewood, CO
30+ employees at Gevo Plant in Luverne, MN
Publicly Traded Since Feb. 2011(NASDAQ Symbol GEVO)
We founded Gevo, Inc. in 2005
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Gevo,Inc.,theworld'sonlycommercialproducerofrenewableisobutanol,announcedthattheU.S.ArmyhassuccessfullyflowntheSikorskyUH-60BlackHawkhelicopterona50/50blendofGevo'sATJ-8(Alcohol-to-Jet).
December, 2013:Gevo Supplies U.S. Army With ATJ-8 Fuel for the Black Hawk Helicopter
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Gevo,Inc.,theworld'sonlycommercialproducerofrenewableisobutanol,announcedthattheU.S.ArmyhassuccessfullyflowntheSikorskyUH-60BlackHawkhelicopterona50/50blendofGevo'sATJ-8(Alcohol-to-Jet).
November 15, 2016:
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Pest Control asNature Intended
28 ©2017Provivi,Inc. CONFIDENTIAL28
MATINGDISRUPTIONTHENEWSTANDARDFORINSECT CONTROL
01
Founded in 2014:
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Science & Environment
Fall armyworm 'threatens African farmers' livelihoods'By Helen BriggsBBC News
6 February 2017 Science & Environment
The armyworm burrows into cobs
Scientists are calling for urgent action to halt the spread of a pest that is destroying maizecrops and spreading rapidly across Africa.
The fall armyworm poses a major threat to food security and agricultural trade, warns the Centre for
CABI
News Sport Weather Shop Earth Travel
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FallarmyworminvadedAfricain2016
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• Fall armyworm & corn earworm mating disruption• Main pest of fresh sweet corn in Florida (30 sprays!)• $600M spent in Brazil corn just for fall army worm
First product: sweet corn in 2018
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Preventative control with mating disruptionArgentina field trials in 2016
Conventional practice
10 insecticide sprays Only 3 insecticide sprays!
0
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24.heinä 3.elo 13.elo 23.elo 2.syys 12.syys 22.syys 2.loka 12.loka
%FA
WIn
festation
Provivi
Provivi (98% mating disruption)
Conventional grower practice
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Jane Goodall
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Diversity of components experiencesminds