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Synthetic biology

Key Points

  • Synthetic biology is a growing discipline that has two subfields. One uses unnatural molecules to reproduce emergent behaviors from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that act unnaturally.

  • Either way, a synthetic goal forces scientists to cross uncharted ground to encounter and solve problems that are not easily encountered through analytical methods. This drives the emergence of new paradigms in ways that analysis cannot easily do.

  • The common goal for both subfields is the use of interchangeable parts to develop new systems to meet performance specifications. These parts must function (to a first approximation) independently. Obtaining interchangeable parts is easier in the macroscopic world than in the molecular world; the principal challenge in synthetic biology is to identify interchangeable parts in the molecular world.

  • The development of living chemical systems and novel organisms allows the scientific community to better understand how the individual chemicals and genes involved in biology interact to form new emergent properties.

  • Synthetic biologists have developed artificial genetic systems that can undergo Darwinian evolution. This has provided insight into the chemical constraints that need to be met by a genetic system.

  • Synthetic biologists have also developed 'toy' organisms and systems, such as an organism that functions as an oscillation system, and a molecular automaton that can interactively play tic-tac-toe with a human.

  • Synthetic biology has used metabolic-pathway design and genetic elements to develop organisms that can synthesize important chemicals, such as precursors for antibiotics and polymers.

  • Truly interchangeable parts at the molecular level have so far only been obtained with nucleic acids. Using amino acids and the secondary structural elements of proteins as interchangeable parts has not yet been possible. Interchangeable genetic elements are possible, although their use is not without complications.

  • Artificial chemical systems that support Darwinian evolution — the bridge between non-life and life — are allowing synthetic biologists to realize the relationship between life and chemistry.

  • The hazards of synthetic biology are open for discussion, because the ability to develop living systems and organisms with novel functions could conceivably be used maliciously.

Abstract

Synthetic biologists come in two broad classes. One uses unnatural molecules to reproduce emergent behaviours from natural biology, with the goal of creating artificial life. The other seeks interchangeable parts from natural biology to assemble into systems that function unnaturally. Either way, a synthetic goal forces scientists to cross uncharted ground to encounter and solve problems that are not easily encountered through analysis. This drives the emergence of new paradigms in ways that analysis cannot easily do. Synthetic biology has generated diagnostic tools that improve the care of patients with infectious diseases, as well as devices that oscillate, creep and play tic-tac-toe.

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Figure 1: Examples of alternative nucleobases.
Figure 2: Branched DNA assay developed by scientists at Chiron and Bayer Diagnostics.
Figure 3: A self-templating system built from peptide units.
Figure 4: Using proteins as interchangeable parts in synthetic biology.
Figure 5: The design and application of the repressilator.

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Correspondence to Steven A. Benner.

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DATABASES

Entrez Gene

Fadd

Gab1

Grb2

Sos2

FURTHER INFORMATION

Benner laboratory

Eric Kool's laboratory page

National Science Foundation's Program in Chemical Bonding

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Glossary

Z-DNA

DNA that exists in a left handed helix rather than the typical right-handed helix of A- and B-form DNA.

G QUARTET

A secondary structure observed in G-rich DNA in which four consecutive guanosine residues bind to each other through interactions in the major groove to form very stable tertiary structures.

REPEATING CHARGE

Where the same ionic charge occurs at the same position of each monomeric subunit of a polymer.

THREOSE DNA

DNA molecules based on the sugar threose rather than ribose.

LOCKED NUCLEIC ACIDS

Nucleic acids containing a CH2 linkage between the 2′OH and 4′ carbon of the ribose sugar.

EPIMERIZATION

Organic molecules can have configurational isomers that have the same number of atoms, and that are bonded in the same way, but that differ in the orientation of the atoms in three dimensions. Epimerization is the spontaneous interconversion of such isomers.

TAUTOMERIC

Isomeric forms of organic molecules in which the same number of atoms are bonded in the same way, except for hydrogen atoms, which are positioned differently.

BUILDING MODULE

A discrete unit used in the construction of a larger structure.

ROTAMERS

(Rotational isomers).Isomeric forms of organic molecules that have the same number of atoms, that are bonded in the same way, but in which the placement of atoms in three dimensional space differs by their rotation around single bonds.

LOGIC GATE

An arrangement of switches used to calculate operations in Boolean algebra; statements are connected into more complicated compound statements by the use of AND, NOT and OR relationships.

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Benner, S., Sismour, A. Synthetic biology. Nat Rev Genet 6, 533–543 (2005). https://doi.org/10.1038/nrg1637

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