PROSPECTS FOR ALGAEin Industrial Biotechnology Targeted manipulation of metabolic pathways ......

PROSPECTS FOR ALGAE

ARI PATRINOS

SYNTHETIC GENOMICS INC.

Products from metabolic engineering

– Ethanol

– 1,3-Propanediol

– Polyhydroxyalkanoates

– Organic acids

– Vitamins

– Amino acids

– Nutritional oils

Improved bioprocess economics

– Product yield (g/g)

– Product concentration (g/L)

– Productivity (g/L/h)

Role of Metabolic Engineering in Industrial Biotechnology

Targeted manipulation of metabolic pathways

Microalgae

Microalgae have exceptionally high oil productivity and growth rates compared to terrestrial plants

• Key issues – Cost vs plant biodiesel feedstock – Low photosynthetic efficiency – Limited genetic tools

• Opportunities

– Improve photosynthetic efficiency using novel photoreceptors – Increase oil content to reduce cost – Tailor fatty acid composition for biodiesel

Algae and CO2 Capture

• In order to grow, algae use sunlight, water and CO2 in the process of photosynthesis

• 1 kg of algae can capture ~2 kg of CO2

• As algae can grow at rates of 30 g/m2/day or more, 1 km2 of algae could capture 30,000 MT of CO2 per year

CO2

Sunlight Seawater

Algae

Carbon Partitioning in Algae

Triose Phosphate

Protein

Carbohydrates

Lipids

CO2

Carbon Partitioning in Algae

Protein

Carbohydrates

Lipids

CO2

Triose Phosphate

Lipids

Hydrocarbons

Alcohols

Hydrogen

CO2 +

CO2 → Biofuels & Biochemicals

Methyl Esters

Limitations of Conventional Metabolic Engineering

• Flux control distributed over the entire pathway

– Amplification of any one gene does not increase pathway flux

• Enzymes from different sources show wide variation in kinetic properties

• In-vitro kinetics may not predict in-vivo behavior of a complex pathway

– Rational selection of best pathway genes difficult

How can we manipulate carbon partitioning?

• Culture conditions – Species selection – Nutrient supply – Growth module design

• Genetic modification

– Classical mutagenesis – Metabolic engineering

• Synthetic genomics – Utilize new genome information – Introduce entire pathways – Test multiple gene configurations – Eliminate side reactions

Synthetic Chromosomes Optimize Production

Cutting-edge technology that enables the design and construction of synthetic chromosomes that optimize production

Anneal overlapping

synthetic oligonucleotides

DNA fragments

Overlapping fragments assembled by

homologous recombination

Chromosome

Transplantation

Synthetic

Chromosome

Synthetic

Chromosome

Anneal overlapping

synthetic oligonucleotides

DNA fragments

Overlapping fragments assembled by

homologous recombination

Chromosome

Transplantation

Synthetic

Chromosome

Synthetic

Chromosome

The Potential of Synthetic Genomics

From reading to writing the genome code

…and synthesizing cells that make useful products

Pharmaceuticals

Substitutes for Petrochemicals

Bio-Energy

T A

G C

Sunlight

Plant Biomass

CO2

DNA Synthesizer

Completely assembled

Synthetic Chromosome

Synthetic Biocatalyst Challenge

London Taxicab

aka. Nature’s Best

Top Speed < 60 mph

Durability ~ 350,000 miles

Formula 1 Racecar

aka. Synthetic Cell

Top Speed > 200 mph

Durability < 800 miles

Goal: 350,000 miles

A New Generation of Designer Cells

Designing food and fuels based on Carbon Dioxide as the source of carbon

Synthetic

Cells

CO2

Plastics

Fuels

Food

Sunlight

Chemicals