Post on 28-Jan-2018
transcript
Innovationbyevolution:Bringingnewchemistrytolife
Frances H. Arnold California Institute of Technology
May 18, 2017
Imag
es c
ourte
sy o
f Shu
tters
tock
Fe
O
SCys
+�
Fe
C
SCys
RR
Fe
N
SCys
R
Carbenetransfer
Nitrenetransfer
X
AATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATDACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCCGCGCGACATAAGGAGTCCTCGTTTCGAGATACGTACGGCATGGTGACACCAGTTGCCCTCTGATTCCCGGAGCCTCTTTGAAAACGTCGAGTCGAATCGAAGTTCGAACCCCGGATCGGGTCCACCAACTTAGAGATGTGTGTGCGCTGACTCAGTCATTTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCAATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGT
AATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATDACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCCGCGCGACATAAGGAGTCCTCGTTTCGAGATACGTACGGCATGGTGACACCAGTTGCCCTCTGATTCCCGGAGCCTCTTTGAAAACGTCGAGTCGAATCGAAGTTCGAACCCCGGATCGGGTCCACCAACTTAGAGATGTGTGTGCGCTGACTCAGTCATTTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGTTAACCACACGTCCCGGATATATTTAATTGGCCGGAGAGTCTCCAATAGCCGTTATTTCCGGATGTGCATAGCTGATTTGACCCATCCGGTACACCAATGGGTCGGACAAATCCCGATTTGATCGTGTGCGCGACATGTCTTCCGGCGACACATGTGTCTCTCACTCCGAGAGATCGGTTAGAGTCTCGGT
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.
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
the internetofliving things
Crowd-sourcing problem solving for 3+ billion years
Humans have altered the biological world using evolution by artificial selection
for thousands of years.
Natural mechanisms for generating sequence diversity are limited
Not so in the test tube…
Imag
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urte
sy o
f Shu
tters
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Sex (DNA recombination) is effective strategy for creating new sequences and functions.
MTIKEMPQPKTFGELKNL...KETSPIPQPKTFGPLGNL...KQASAIPQPKTYGPLKNL...WRRRGIPGPLGYPLVGSF...WIRKGVKGPRGLPFLGVI...FIRKGIKGPRGFPGIGML...WIRKGVKGPRGFPFFGVI...WIRKGVKGPRGFPFFGVI...WMRKGIKGPRGLPFFGII...WMRKGVKGPRGRPFVGVL...WRRRGVVGPMGFPVLGVF...REKIGLSGPEPHWFLGNL...REKIGLTGPEPHWFMGNL...RSSIGIPGPPVHWLWGNL...KVSKYPKGPLPLPFIGNI......
Sex with molecules
Performance
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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
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.
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…
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
Directed evolution converted this protein into a highly active catalyst for silicon-carbon bond formation…
0
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WT M100D V75TM100D
V75TM100DM103E
TTN
97%ee
>99%ee
>99%ee
>99%ee
(act
ivity
)
...inside living cells.
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
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
Gevo,Inc.,theworld'sonlycommercialproducerofrenewableisobutanol,announcedthattheU.S.ArmyhassuccessfullyflowntheSikorskyUH-60BlackHawkhelicopterona50/50blendofGevo'sATJ-8(Alcohol-to-Jet).
November 15, 2016:
Pest Control asNature Intended
28 ©2017Provivi,Inc. CONFIDENTIAL28
MATINGDISRUPTIONTHENEWSTANDARDFORINSECT CONTROL
01
Founded in 2014:
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
FallarmyworminvadedAfricain2016
• 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
Preventative control with mating disruptionArgentina field trials in 2016
Conventional practice
10 insecticide sprays Only 3 insecticide sprays!
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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
Jane Goodall
Diversity of components experiencesminds