pistoia alliance us conference 2015 - 1.2.3 innovation in other industries - wayne mitchell

Philadelphia , 13.09. 2015

Wayne Mitchell Model Systems Lanzatech

[email protected] & Copyright 2015 Lanzatech. All rights reserved

An Integrated Model Organism Omic’s Infrastructure

( on a budget )((a tiny budget))

(((really small)))

Dr. Jennifer HolmgrenCEO (2010 -- )

Dr. Sean SimpsonFounder & CSO

Lanzatech founded 2005

Confidential & Copyright 2015 Lanzatech. All rights reserved

Founded in New Zealand


"a number 8 wire mentality"

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• Series A: Khosla Ventures – $US 12M in 2007• Series B: Qiming Ventures – $US 18M in 2010• Series C: MLSF – $US 56M in 2011• Series D: Mitsui-$US 112M in 2014

Current Valuation: 450 M

Strong Support from Investors

Leads:


Fuel production has been demonstrated with a wide range of available waste gas resources

Gas Composition

Gas-to-liquid Conversion

H2

CO

Industrial Flue Gas

e.g. Steel Mill

SyngasMunicipal SolidWaste (MSW)

Steam Reformed

Methane (NG)e.g. Biogas

Forest products

Flexible CO:H2 Ratio. Many feedstocks


H2

CO

Gas Compositio

n Industrial Flue Gas

e.g. from Steel Mill

SyngasMunicipal SolidWaste (MSW)

Steam Reformed

Methane (NG)e.g. Biogas

Forest product

s

Gas-to-liquid Conversion

Focus on industrial waste gas


Carbon Monoxide from steel mill

7Confidential & Copyright 2015 Lanzatech. All rights reserved

Carbon Monoxide from steel mill

8

Gas feed stream

Gas reception

Recovery

Producttank

• Bioremediation • Green Chemistry• Non-food biofuel

Fermenttion


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Large portfolio of issued patents

Basic Science EngineeringConfidential & Copyright 2015 Lanzatech. All rights reserved

Pre-commercial Demo plant

16,000 L Vessel

Demo

Bench top 1-10L vessels

CSTR

Scalable design Up to 100L capacity

LabPilot

Glenbrook NZ Steel mill pilot

2 x 500L Vessels

PilotStrain Development

Commercial scale plants under construction

Process is robust, scalable and proved


Steel Mills (>5M Tpa)

Steel Mill Gas Feedstock is Scalable


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Nature: the real innovator

A “Black Smoker”Confidential & Copyright 2015 Lanzatech. All rights reserved

Clostridium sp.

Clostridia autoethanogenum

Brown et al Biotechnology for Biofuels 2014, 7:40 Confidential & Copyright 2015 Lanzatech. All rights reserved

C. Autoethanogenum can fix noxious carbon

Wood-LjungdahlPathway

Brown et al Biotechnology for Biofuels 2014, 7:40 Lars Ljungdhall


Ethanol

IsopropanolAcetone

1-butanol

2,3-Butanediol

MEK

2-butanolisoprene

succinate

CO/H2

Gas to Fuel and Chemicals

biodiesel

lactate

DiscoveryLab-scale

Cont.Ferment.

Pilot/Demo

Pyruvate

Acetyl-CoA

Fatty Acids,Terpenoids


Clostridia autoethanogenum

Brown et al Biotechnology for Biofuels 2014, 7:40 Confidential & Copyright 2015 Lanzatech. All rights reserved

LanzaTech is the first company to demonstrate 2,3-butanediol (2,3-BDO) production by gas fermentation

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2,3 BDO: a 4-carbon first


We want to engineer C. auto


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The tyranny of model organisms

G.P. Box

“All models are wrong, but some are useful”


Ilumina myseq/ hyseq: > 50 contigs454: > 50 contigsIllumina + 454: > 50 contigs

PacBio SMRT2: Closed Genome, 1 contig.

PacBio SMRT2 for de novo sequencing*

*Collaboration with ORNL: Brown et al Biotechnology for Biofuels 2014, 7:40


PacBio SMRT2 + one NGS for polish

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6

17

9

0

0

4

3

Fuse 2 orfs Split an orf into 2 orfs

Resolve frameshift/ pseudo gene Create frameshift/ pseudo gene

Major addition (10 AA - > 100 AA) Major deletion

Minor addition Minor deletion

Ion Torrent resequencing* predicted 50 discrepancieswith PacBio; these were confirmed by Sanger.

* Dr. Richard Allcock UWA.

NGS polishing step had a small but significant impact on our view of the genome


Reannotation of the Genome


transcriptome

metabolomeproteome

Functional omicsCollaboration with University of Queensland, PNNL & ORNL


We few, we happy few


Asela Dassanayake(Comp Bio Scientist, MS Bioinfo)

Vini Reynoso(Comp Bio Research Associate& Aspiring graduate student)

James Daniell(Almost a PhD, U. Auckland)

Stuart Bradley(Honors, Comp Sci. U.Auckland)Not presenting today Supporting ~ 20 scienctists

1:7


The 42% SolutionAAbbatiello, SusanAnerson, Kristian

BBanks, Eric *Bittker, JoshuaBoehm, JesseBrandes, Aaron *Bray,Mark-Anthony *CClemons, Paul *Cowley, Glenn SCuomo. ChristinaDDesjardins, Christopher *EEpstein, CharlesFFromer, Menachem *GGoldberg, Jonathan *Greulich, Heidi

H

JJacobs, SuzanneJaffe, JacobKKamentsky, Lee *LLatorre, IsabelLogan, David *MMadison, JonMcGuire, Abigail *NNeafsey, DanielOO’Dushiane, ColmPPan, JenPark, Daniel *Patterson, Nick *

* COMPUTATIONAL SENIOR INVESTIGATORS (14/33)

R

SSchaffber, Stephan *Schenone, MonicaT

U

VVetere, Amedeo

WWagner, BridgetWahiby, Carolina *X

YYozwiak, NathanZ


The Knowledge Cycle

ExperimentalScience

InformationScience

Statistics, Visualization,Modeling

ITERATE

Describe & Discover Organize & Retrieve Integrate & Understand

Efficient, ‘laminar’ data flow



Return on precious R&D dollars goes down

Value is Unrecognized

… becomes inefficient ‘turbulent’ data flow.


Our Informatics Infrastructure strategy: Strength in Numbers

“A man alone ain’t got no bloody f*****’ chance”

Hemingway (Ernie, not Dom)


The ‘Generic Model Organism Database’ Community


GMOD Open Source Tools

The Vasa: a cautionary tale

Launched: Sunday, the 10th of August, 1628Lost: Sunday, the 10th of August, 1628



Thrift! Thrift !

Our First Server literally built From cannibalized junk

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Thrift 2.0

Hardware Layer

Virtualization Layer*

HP ProLiant DL380p Gen8 server with two Intel Xeon E5-2650 0 @ 2.00GHz processors, 256GB RAM, and dual 2-port 10GB NICs; a 22TB Nimble CS460 SAN which itself has dual 10GB NICs and redundant controllers, all connected to dual 10GB per port Cisco Nexus 5672 core switches


Lessons?


1. Survive

Lessons?


1. Survive2. Throw nothing away

Lessons?


1. Survive2. Throw nothing away3. Take advantage of open source tools

Lessons?


1. Survive2. Throw nothing away3. Take advantage of open source tools4. Advocate (internally and externally) for

adequate resources, hard and soft!

Lessons?


1. Survive2. Throw nothing away3. Take advantage of open source tools4. Advocate (internally and externally) for

adequate resources, hard and soft!5. Start-up in New Zealand.

Thank you !


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