SynBio for the Environment

Víctor de Lorenzohttp://www.cnb.csic.es/~meml

Centro Nacional de Biotecnología (CNB)Consejo Superior de Investigaciones Científicas (CSIC)

Madrid (Spain)

OurOur scenarioscenario ……

Accessing the catabolic landscape Repsol - YPF Oil Refinery. Puertollano (Spain)

CH3Cl

Cl

Cl

ClCl

NO2

CH3 (CH)nCH3

OHCH3

Cl

CH3

NO2

NH2

CH3

OH

Recalcitrance Mineralization

BiotransformationCo-metabolism

BiotransformationN, S, electron acceptor

CO2+

H2O

Engineered Biological agents for environmental application

• In situ biodegradation

• Bio‐transformation

• Detection

• Immobilization

Service Molecular Biology(hypothesis-driven experimentation)

Partnership Systems Biology(data-driven information mining;model-driven experimentation)

Leadership? Synthetic Biology(forward design of biological properties)

Physics, Computation and Engineering

From servants to Masters of the (biotech) House?

Proposition #1

The criterion for identifying newscenarios associated to the application of Synthetic Biosystemsis not the way the agent isengineered, but the divide betweenfamiliar and non‐familiar Biology.

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Synthetic Biology

Genetic Engineering

The roadmap from Genetic Engineering to Synthetic/Non‐natural MO 

E. E. colicoli NissleNissle 1917 1917

Natural bacterium

Streamlined genome

Genome-less cells

Synthetic DNAfragments

SyntheticGenomes

Viral vectors

Yeast vectors

Plasmid &Transposonvectors

Vesicles/artificial cellsXeno-Nucleic acids (XNAs)

Orthogonal cellsAlternative information-bearingmolecules / genomes

Streamlined genome

• Orthogonal ribosomes• Alternative/expanded genetic codes• Proteins with non-natural amino acids

Fam

iliar B

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gy

Non-familiar Biology

The 10 questions on environmental risks borne by Engineered/synthetic/non-natural microorganisms (SEMs)

1. Can SEMs colonize and eventually takeover natural microbial communities?

2. Is there a chance that SEMs enter new niches that natural bacteria cannot?

3. Might SEMs go into a stage of uncontrolled growth?

4. What are the chances of horizontal transfer of the synthetic genes to novel recipients?

5. Is there a tradeoff between safety and biotechnological efficacy of SEMs?

6. Could traits engineered in SEMs evolve towards virulence or other deleterious behavior?

7. Are there scenarios of SEMs capable of damaging life or property?

8. What is the environmental fate of synthetic genes?

9. Are there chances of malicious misuse of SEMs

10. Should SEMs be endowed with traits to increase their safety and predictability?

Proposition #2

The biggest challenge of SB re. Environmental applications is the projection of stochastic behaviour ofindividuals into populationperformance.

Projection of stochastic-single cell events intopopulation behaviour

The Complexity Pyramid

Landscape

Habitat

Biofilm

Niche

Community

Population

Cell

GenomeGenome

Metabolic networks

Genetics, Genomics

Transcriptomics, Proteomics,Metabolomics, Phenotype

Community Profiling,Tracer Technology

Process Analysis

Activities,Microprobes

Experimental Approaches

Global Processes, Interactions

Community Dynamics,Activities, Invasions

Metabolic NetworksAnd Interactions

Local Interactions

Gene expression, Regulation

Cellular Activities

Biologicalquestions

Proposition #3

For the next 10 year (at least), frontline Environmental Biotechresearch will rely the combination ofMetagenomics with SyntheticBiology.

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Culturablefraction

Non-culturablefraction

DNA

Slow growth

Fast growth

Activity

mining

Exper

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Orthogo-

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Chassis���Reduction

refactoring

Functionalmodule

Implantation

Animal, Plant, Synthetic

CELL FACTORY���

Combining Synthetic Biology with Metagenomics

Proposition #4

Synthetic Biology will bring about a transition from a Geno‐centricEnvironmental Biotech to a Chemo‐centric discipline

The geno-centric syndrome

DNA

RNA

Proteins

The geno-centric syndrome

Metabolism

DNA

RNA

Proteins

The ongoing shift in understanding live systems

The selfish metabolism

Proposition #5

Adress public debates with a historical perspective:

• Learn from past controversies• Study mistakes and try better• Do not alarm the public• Find societal allies

Boston 1846William Morton

Questions raised by every new groundbreakingTechnology related to Life Siences

• What is the Science behind?

• Is it safe? ¿Risks?

• Who owns intellectual property? 

• Who benefits?

• Should it be regulated / controlled? By whom?

• Natural vs. Non‐natural: Are we playing God? 

and by all means…

Do not play the arsonist fireman!

Paris, 1800 Knoxville, 1990

Centro Nacional de Biotecnología (CNB)Consejo Superior de Investigaciones Científicas (CSIC)

Madrid‐Cantoblanco (Spain)

THANKS!THANKS!

Proposition #5

Think BIG! For the first time wecan entertain scenarios forengineering global biocatalysisinterventions

Artificial cells(Semi) Synthetic cellsRefactored cellsEngineered microorganismsMutant strainsNatural isolates

Added value productsIndustrial biotransformations

Waste treatmentin situ Bioremediation

Global Catalysis

CATALYST TYPE

CONTAINMENT OUTCOME

Uncontained dPhysically contained d

Genetically contained d Conditional viability y

Free release d

Test t

ube,

flask

Quantity of reaction substrate(s)log scale (gr)

Reacto

r

Ferm

entor

Areawide

Global

100 -102 103 -105 106 -109 1010 -1012 >1013

SIZE MATTERS

Proposition #6

Look at societal/ethical debates with a historical perspective –do not re-invent the wheel by over-emphasizing issues thatwere tackled time ago

Boston 1846William Morton

Questions raised by every new groundbreakingTechnology related to Life Siences

• What is the Science behind?

• Is it safe? ¿Risks?

• Who owns intellectual property?

• Who benefits?

• Should it be regulated / controlled? By whom?

• Natural vs. Non-natural: Are we playing God?

Proposition #7

Pursue societal allies andidentify end-users beyondlobbing/impressing/entertainingthe powerful

Paris, 1800 Knoxville, 1990

This paper was produced for a meeting organized Health &Consumers DG and represents the views of its author on the  subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumers DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.