Synthetic Biology for Synthetic Chemistry

• Published in: ACS chemical biology Vol. 3; no. 1; pp. 64 - 76
• Main Author: Keasling, Jay D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.2008
• Subjects: Antimalarials - chemical synthesis; Antimalarials - chemistry; Artemisinins - chemical synthesis; Artemisinins - chemistry; Chemistry, Organic - methods; Chemistry, Organic - trends; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli - metabolism; Genetic Engineering - methods; Genetic Engineering - trends; Molecular Biology - methods; Molecular Biology - trends; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Artemisinin: A sesquiterpene lactone endoperoxide extracted from Artemisia annua L that is highly effective against multi-drug-resistant Plasmodium spp; Tunable intergenic region (TIGR): Untranslated region between two coding regions of a multicistronic mRNA, which contains sequences that control mRNA processing and translation of one or both of the surrounding coding regions; Synthetic biology: The design and construction of new biological components, such as enzymes, genetic circuits, and cells, or the redesign of existing biological systems; Metabolic burden: The consumption of macromolecule precursors and energy due to the expression of foreign genes in a cell; CAD: Computer-aided design; Operon: A group of genes under the control of a single promoter or multiple promoters; Metabolic engineering: The manipulation of intracellular metabolic reactions for the production or degradation of a target chemical; Internal ribosome entry sequence (IRES): A sequence between two coding regions on a multicistronic mRNA that allows a eukaryotic ribosome to initiate translation of the 3′ coding region; All-or-none induction or expression: The induction of an inducible promoter to full strength in only a fraction of the cells of a population, the fraction dependent on the concentration of the inducer in the medium
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/cb7002434

The richness and versatility of biological systems make them ideally suited to solve some of the world’s most significant challenges, such as converting cheap, renewable resources into energy-rich molecules; producing high-quality, inexpensive drugs to fight disease; and remediating polluted sites. Over the years, significant strides have been made in engineering microorganisms to produce fuels, bulk chemicals, and valuable drugs from inexpensive starting materials; to detect and degrade nerve agents as well as less toxic organic pollutants; and to accumulate metals and reduce radionuclides. The components needed to engineer the chemistry inside a microbial cell are significantly different from those commonly used to overproduce pharmaceutical proteins. Synthetic biology has had and will continue to have a significant impact on the development of these components to engineer cellular metabolism and microbial chassis to host the chemistry. The ready availability of more well-characterized gene expression components and hosts for chemical synthesis, standards for the connection of these components to make larger functioning devices, computer-aided design software, and debugging tools for biological designs will decrease both the time and the support needed to construct these designs. Some of the most important tools for engineering bacterial metabolism and their use for production of the antimalarial drug artemisinin are reviewed.