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Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

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Page 1: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Synthetic Biologyfor Synthetic Drugs and Fuels

Jay Keasling

University of California, Berkeley

Lawrence Berkeley National Laboratory

Page 2: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Malaria

Page 3: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

NCl

NHH3C

H3C

H3C

Chloroquine-based drugs

Source: Roll Back MalariaWorld Malaria Report 2005

Page 4: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Artemisininthe best anti-malarial drug

O

O

O

OO

H

HH

Page 5: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Current process

Artemisinin

O

O

O

OO

H

HH

Plant synthesis

Purification

Artesunate

O

O

H

H HH

OO

OH

O

OH

OO

O

H

H HH

OO

OH

O

OH

ArtelinateArteetherArtemether

O

O

OMe

OO

H

HHO

O

OEt

OO

H

HH

ChemicalConversions

Page 6: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Artemisinin demand analysis

Source: Boston Consulting Group

247 in 2006

Malaria Cases (millions)

GMAP target135 in 2020

Total ACT Demand

Millions of treatments

ACTs delivered (actual)

Demand forecasts from other groupsBCG Demand forecast scenarios

ACTs delivered

50

100

150

200

250

300

350

03 04 05 06 07 08 09 10 11 12 13 14 15 16 17 18 19 20

Page 7: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Artemisinin price swings

Artemisinin prices($/kg)

Food prices (indexed to Jan 2002)

Artemisininprices

Commodityfood prices

2002 2003 2004 2005 2006 2007 2008 2009

Source: Boston Consulting Group

Page 8: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Artemisinin supply

50

100

150

200

250

300

350

03 04 05 06 07 08 10 11 12 13 14 15 16 17 18 19 20

Tonnes of Artemisinin

Variable production

Stock from previous yearHistoric production

Demand

Minimum production floor

09

Source: Boston Consulting Group

Page 9: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Current process

Artemisinin

O

O

O

OO

H

HH

Plant synthesis

Purification

Artesunate

O

O

H

H HH

OO

OH

O

OH

OO

O

H

H HH

OO

OH

O

OH

ArtelinateArteetherArtemether

O

O

OMe

OO

H

HHO

O

OEt

OO

H

HH

ChemicalConversions

Page 10: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Microbial process

Artemisinin

O

O

O

OO

H

HH

Microbial synthesis

Purification

Artesunate

O

O

H

H HH

OO

OH

O

OH

OO

O

H

H HH

OO

OH

O

OH

ArtelinateArteetherArtemether

O

O

OMe

OO

H

HHO

O

OEt

OO

H

HH

ChemicalConversions

Page 11: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Microbial synthesis of artemisinin

Page 12: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Improvements in yield lower

artemisinin costs

Current cost of API $1.00/g

Cost with new process $.10/g

Page 13: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Research, Development & Delivery

Keasling Laboratory

Amyris Biotechnologies

Page 14: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Global Warming and

Energy Security

Page 15: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Petroleum-based transportation fuels

CO2

Page 16: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Corn to Ethanol

CO2

CO2

Page 17: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Corn to Ethanol

CO2

CO2

Page 18: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

CO2

CO2

Corn to Ethanol

Page 19: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Corn is not an ideal energy crop

• Water requirements

• Fertilizer requirements

• Bred to be a food crop

Page 20: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

CO2

CO2

Biomass to Ethanol

Page 21: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

US annual biomass inventory 1.3 billion tons

Forest12.8%

Urban waste2.9%

Manure4.1%

Grains5.2%

Crop residues7.6%

Soy6.2%

Wheat straw6.1%Corn stover

19.9%

Perennial crops35.2%

From: Billion ton Vision, DOE & USDA 2005

Page 22: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

5

6

7

Bill

ion

Bar

rels

of

Oil

Eq

uiv

alen

ts

0

1

2

3

4

2007 US Imports

2007 US Domestic Production

Fuel yields from biomass using mid-term conversion technology

Energy from burning biomass4.4

2.5

1.9

3.5

How much fuel can we produce from 1.3 billion tons of biomass?

2007 US PetroleumConsumption

7.6

Page 23: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

CO2

CO2

Biomass to Ethanol

Page 24: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Ethanol is not an ideal fuel

Page 25: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Repurposing a microbial production platform

Page 26: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Repurposing a microbial production platform

Biofuel

Page 27: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Engineered microbes produce oil and advanced biofuels

Page 28: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

Biomass to advanced transportation fuels

CO2

CO2

Page 29: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

The Joint BioEnergy Institute (jbei)

CO2

CO2

Page 30: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

jbei: a Bay Area Partnership

Page 31: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

jbei’s Research Program

CO2

CO2

Page 32: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

jbei: a single location

Page 33: Synthetic Biology for Synthetic Drugs and Fuels Jay Keasling University of California, Berkeley Lawrence Berkeley National Laboratory

jbei: an incubator for great ideas and the green economy

Biofuels Companies

Feedstock Companies

Chemical Companies

Petroleum Companies

Plant Genetics

Companies

Biotech Companies