GenomaticaSustainable Chemicals

GenomaticaSustainable Chemicals

Genomatica

Pacific Rim SummitDecember 7-9, 2014Mark J. Burk, CTO

Genomatica: Sustainable ChemicalsTechnology Provider to the Chemical Industry

• Exact same chemicals

• Better economics

• Equivalent performance

• Reduced energy use

• Lower carbon footprint

• Feedstock diversification

Regionally

Advantaged

FeedstockBasic & Intermediate

Chemicals

Existing products

sold globally

Tolerance

High titerHigh

yield

High

rate

High Performance

Organisms and Processes

Robust unit

operations

Three Pillars of Bioprocess DevelopmentStrain design guided by process design

Simple BC Fermentor

6.6 m

Tower diameter

T-T

27.4 m

3m

Skirt

Distance

from End

EngineeredCells

Air

Exhaust Gas

SugarsMedia

Purified ChemicalMeet industry specs

Optimize fermentationconditions

Optimize recovery and purification

Optimize sugar to chemical flux

Strain Engineering

to Produce Chemical

Fermentation

DevelopmentRecovery/Purification

PentosePhosphatePathway

Ac-CoA

Gly

coly

sis

Chemical

ChemicalPathway

F6P

G3P

Feedstock

Existing

CentrifugeUltrafiltration

Evaporation

Lights Distillation

Cells/Solids

Water

UF Retentate

Lights

Purified

BDO

Sucrose/

Glucose

Fermentation

Nanofiltration

NF Retentate

Ion Exchange

BDO Distillation

Sterilizer

Residue

Cell Removal Salt/Media Removal

Purification

Dewatering

Water

Hydrogenation

Heavies Removal

Existing Existing

Existing

New

New

Platform Attributes:

Computer-aided design for biology (since 2000)

Enables focused efficient experimentation

Integrated bioprocess design, scale-up, economics

Rapid, cost-effective, lower risk development

Process

Engineering

Predictive

Computer Models

Experimental

Biotechnology Biotechnology

Platform

Advantaged

Process

Technology

Integrated Bioprocess Technology Platform

Confidential

Commercial Strain Engineering Challenges

Commercial scale fermentations introduce unique challenges

Fast growth,

Minimal lag

in prodn

Increase rateImproved enzymes

Lower by-products

Sugar uptake rate

Aeration, co-factor balance

Delay production slowdownNutrient limitation

Osmolarity

Tolerance, stress

Enzyme inhibitionGenetically stable hostFully integrated – no plasmids

Constitutive expression – no IPTG

Commercial conditionsTolerate heterogeneous aeration

Perform at high pCO2 (0.3-0.4 atm)

Complete sugar consumption

Minimal defined mediaLowest cost, ensure cellular

requirements satisfied,

low downstream impact

Titer

(g/L

)

Target

Titer

Time

Sugars

1,4-Butanediol(Biobased BDO)

BDO-producing E. coli

Genomatica technology platform has enabled commercial targets

The GENO BDOTM Process in Engineered E. coli

• 1.4 M ton/year

• PBT, TPU, Spandex

• Direct production from sugars

Improved BDO Process = Lower Production Costs

0

20

40

60

80

100

120

140

0 12 24 36 48 60 72

BD

O T

ite

r (g

/L)

Time (h)

Dec, 2013

Nov, 2012

Apr, 2012

Feb, 2012

May, 2011

Mar, 2011

Jan, 2009

T = 140 g/L

R = >3 g/L/hr

Y* = >102 %

Y* = % of commercialization yield target

E. coli

Glycolysis

TCA

Cycle

BDO

PathwayBDO

E. coli

Sugars Glycolysis

TCA

Cycle

BDO

Pathway

140 g/L

BDO

CO2

Biomass

4HB

Ethanol

Acetate

GABA

Glutamate

Others

Unknown

1,4-BDO

CO2

Biomass

4HB

BDO

CO2

Biomass

4HB

Ethanol

Acetate

GABA

Glutamate

Others

Unknown

1,4-BDO

CO2

Biom.

LowerBy-products

LowerCost

($ / Ton, 50KT Capacity)

($ / lb)

2009 2012 2015 2018 Leading Petro

Technology

Indirect Bio-BDO

TechnologyBDO Price

Historical

Base Case Projection

Upside Case Projection

North America

Europe

Price

Cash Cost

GENO BDOTM Process Commercialization Journey 5 years from concept to commercial production (>4k tons produced & sold)

BDO Producing Organisms – 2008 Purified BDO – 2009 3,000 Liter Piloting – 2010

Commercialization – 2012-13…

600,000 L

Integrated Demo Plant – 2011 Shipping Tons at a Time – 2011

13,000 L

MBI

Tate & Lyle DuPont Tate & Lyle

Robust Scale-Up / Scale-Down of 1,4-BDO ProcessUnderstanding and testing of key scale parameters

Consistent fermentation performance across lab, pilot, demo, and commercial scales

Low variability over 50+ large scale fermentations process robustness and predictability

Robust Performance at Commercial-Scale

0%

20%

40%

60%

80%

100%

120%

0 10 20 30 40 50

Batch No.

Percent Average Commercial Scale IRR'

0%

20%

40%

60%

80%

100%

120%

0 10 20 30 40 50

Batch No.

Percent Average Commercial-Scale Yield

Top 5 Fermentation RunsFermentation Run

Consistent Scale-up to Commercial

13,000L

Demonstration

ScaleCommercial

Scale

~ 50x

scale-up

Commercial vs Demo

Titer 98%

Rate 104%

Yield 100%

Average Fermentation

Performance

( ~50 runs at commercial

scale vs. average demo

scale)

Consistent Performance Across Development Scales

0%

30%

60%

90%

120%

2L 30L 13kL

Tit

er,

g/L

BD

O(a

s %

of 2L)

0%

40%

80%

120%

160%

2L 30L 13kL

Rate

, g

/L.h

r (a

s %

of 2L)

0%

30%

60%

90%

120%

2L 30L 13kL

Yie

ld, g

/g(a

s %

of 2L)

Lessons Along the Way

Biology has a lot to offer – direct conversion of alternative primary feedstocks to chemical products

Commercializing industrial biotechnology for chemicals is not easy:

• Commercializing new-to-the-world technology in a conservative mature industry

• Achieving competitive economics – both organism and process performance are important

• Validating value proposition (ROI) to justify development investment

• Financial committment – it will always take longer and cost more than you think

• Hitting performance guarantees and meeting industry specs

• Chemical industry inexperience with fermentation and Ag feedstocks

Feedstock flexibility is critical – global industry vs regional feedstock advantages

• Conventional sugars – available but volatile prices, food vs chemicals, low cost limited to US, Brazil, Thailand, India

• Biomass sugars – not ideal for fiber/polymer grade chemicals, sugar quality and cost remain major challenges

• C1 feedstocks – lower cost is attractive, but technically more challenging to engineer strains/processes

Technology platform matters – nature is complex; drive down timelines/resources to achieve comm. perf. targets

Partnerships are key – feedstock, scale-up, engineering, commercial ops, product distribution, marketing, sales...

Innovative Chemical Processes via Biotechnology

Genomatica’s Innovation Center in San Diego, California – over 115 employees

Thanks!

“Innovation distinguishes between a leader and a follower.” Steve Jobs, Apple CEO