Biology Reference
In-Depth Information
10
CHAPTER
Drug Discovery and
Development via Synthetic
Biology
Ryan E. Cobb, Yunzi Luo, Todd Freestone and Huimin Zhao
University of Illinois at Urbana-Champaign, Urbana, IL, USA
INTRODUCTION
Since the expression of the first synthetic gene in 1977, the pharmaceutical sector has been
revolutionized with the manufacturing of protein therapeutics such as hormones, vaccines,
antibodies, blood factors, and therapeutic enzymes. The industry is poised for another
revolution as advancements in synthetic biology allow the production of bioactive
compounds in nonnative hosts. Molecules from natural sources have proved to be an
important source of new pharmaceuticals, and newly discovered natural products have been
shown to be promising in the treatment of cardiovascular disease, cancer, and infectious
diseases.
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Sources for such compounds are equally diverse, including microbes, plants,
marine sources, and even insects. Because natural products of interest often have complex
structures, their chemical synthesis can be impractical. Additionally, they are formed in only
low concentrations in their natural producer, preventing sustainable and economical
extraction. For these reasons, optimizing natural product pathways in genetically
tractable and cultivatable hosts have been an attractive alternative.
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However, heterologous production of small molecules has often been avoided for several
reasons. Often the complete metabolic pathways are not known. Even if the necessary genes
are known, protein expression and enzyme function may be severely diminished in the
nonnative environment. Another problem is the numerous permutations that must be
tested when modulating protein expression throughout a pathway. Synthetic biology offers
both computational and experimental tools that help to overcome these problems. In
addition, the discovery of new natural products is possible with synthetic biology,
increasing the influence the field will have on future pharmaceutical development.
TOOLS FOR PATHWAY DISCOVERY AND ENGINEERING
Synthetic biology is built upon the concept of biological systems as machines that can be
designed and engineered to perform a desired objective, as in the synthesis of a drug or drug
candidate molecule. The success of such an approach is predicated on two key concepts:
first, an extensive set of diverse parts from which to construct such machines; and second,
sophisticated techniques by which to assemble and engineer these parts into working
pathways. The former has been significantly aided by the rapid development of
