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Synthetic Biology
Synthetic biology focuses on the manipulation of biological components to form new systems or the generation of living systems with synthetic parts. The canonical idea of synthetic biology is the creation of new life, but recently it has come to include bioengineering in terms of the use of interchangeable components to give novel outputs. In the search for modular parts, it is most facile if the building blocks contribute independently to the function of the whole unit so that the modules can be recombined in predictable ways. It is useful for synthetic biologists to define “life”: in this context, to be alive an organism must be capable of Darwinian evolution – genetic mutation, self-replication and inheritance of mutations.

Synthetic Cells
J. Craig Venter’s group has created the first “synthetic” cell – the first cells to exist with fully synthetic DNA. Venter was able to manipulate the synthetic genome to dictate the proteins expressed in the organism. Note that these were not fully synthetic cells – but that the synthetic DNA was able to take over all metabolic processes necessary for cell survival and proliferation.

DNA as interchangeable parts
DNA is composed of repeating modular units consisting of an anion phosphate group that forms the polyanion backbone, and nucleotide base pairs that engage in Watson-Crick base pairing to form the double strand. Because the molecular recognition of DNA is mostly based on the polyanion backbone, the nucleotides can be modified without altering the structural integrity of the DNA. Steven Benner’s group has generated an artificial genetic alphabet of eight new base pairs that can be amplified by polymerase chain reaction; this indicates that these base pairs can be used in systems that undergo Darwinian evolution.

Amino Acids
Amino acids are poor modular building blocks because they don’t act independently and there is a fundamental lack of understanding about the relationship between linear amino acid sequences and the folding and functionality of proteins. Chemical biologists have been able to create small peptide secondary structures through rational design such as alpha helices based on the manipulation of hydrophobic packing interactions.

Protein Secondary Structure
Modules consisting of protein secondary structure can be designed to perform specific functions; for example, it has been demonstrated that alpha helices can be used as functional peptide catalysts. The Ghadiri group has created a template peptide that promotes the ligation of two modified helices by bringing the helices into close proximity by specifically designed hydrophobic interactions of the helices with the template.

Folded Proteins
Fully folded proteins can be combined in novel ways to generate specific non-natural outcomes. This is highly useful commercially from drug development to the production of polymers – one can imagine the economic benefits if scientists can design systems in which proteins catalyze reactions without the necessity of excessive human intervention to produce commercially relevant materials. For example, the Keasling group has developed a series of proteins that catalyze conversion of acetyl co-A, a common cellular metabolite, into a precursor for the potent antimalarial drug artemisinin.

Modifying Molecular Switches
Signaling pathways can be modified to be turned on or off by non-natural ligands or inputs to the system. For instance, systems can be modified so that they are autoinhibited by non-natural proteins that release their inhibition upon binding with a specific molecule that is different from the natural signaling molecule of the path. This allows new approaches to studying signal circuits specifically and with user-designed inputs.