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Nat Rev Microbiol. 2016 Mar;14(3):135-49. doi: 10.1038/nrmicro.2015.24.

Synthetic biology to access and expand nature's chemical diversity.

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Department of Biochemistry, Molecular Biology, and Biophysics and the BioTechnology Institute, University of Minnesota Twin Cities, Saint Paul, Minnesota 55108, USA.
Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California 94158, USA.
Departments of Chemistry and Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida 33458, USA.


Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology--including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits--and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products.

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