Gene Systhesis Empowers Metabolic Engineering

Metabolic Engineering

Metabolic Engineering involves introducing novel or recombinant genes or genetic circuits into host cell genomes in order to modify or introduce new metabolic pathways. Metabolic Engineering is typically used to solve a problem by turning E. coli or other microbiological hosts into efficient “factories” optimized to perform specific tasks. Metabolically engineered organisms can produce a desired biomolecule with higher yield and purity than non-genetically engineered organisms. Metabolic engineering can take advantage of existing biological systems such as quorum sensing and conditional gene expression feedback loops to allow cells to act as sensors or detoxifiers of environmental pollutants. Genetically engineered bacteria can be created through the use of gene synthesis and genome editing techniques and can be used in a variety of research, biomedical and industrial applications.

GenScript Services for Metabolic Engineering Research

• GenBrick™ DNA Building Blocks for Synthetic Biology: 8-15 kb long DNA constructs in just 23 business days
• OptimumGene Codon optimization: ensure efficient expression of all genes in your pathway
• GenCRISPR™ genome editing services, including free all-in-one vectors and a free online gRNA design tool

Featured Publications in Metabolic Engineering

• Kallio et al. An engineered pathway for the biosynthesis of renewable propane. Nat Commun. 2014 Sep 2;5:4731. Free Full Text
• Xu et al. Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11299-304. Free Full Text
• Xue et al. Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica. Nat Biotechnol. 2013 Aug;31(8):734-40. Free Full Text
• Nguyen et al. Redirection of metabolic flux for high levels of omega-7 monounsaturated fatty acid accumulation in camelina seeds. Plant Biotechnol J. 2014 Jul 26. doi: 10.1111/pbi.12233. Free Full Text

Search or browse peer-reviewed publications on metabolic engineering that cite GenScript services & products.

GenScript-Sponsored teams win awards for new Genetically Engineered Bacteria

The International Genetically Engineered Machine (iGEM) Competition showcases synthetic biology and metabolic engineering innovations that create new tools for research, healthcare, energy, or environmental applications. For example, in the 2014 Jamboree, the GenScript-sponsored undergraduate team from Eindhoven in the Netherlands won a gold medal and the award for Best New Application for their work to make genetically-engineered bacteria more resilient for use in environmental or biomedical applications, by designing two Clickable Outer Membrane Proteins that can allow bacteria to be easily encapsulated by a protective, biocompatible PEG shell.

Case Studies: Creating Genetically Engineered Organisms to Express Novel Metabolic Pathways

More efficient synthesis of valuable biomolecules (natural products). Metabolic engineering enables the efficient production of naturally occurring compounds that have valuable research or industrial uses. Before gene synthesis technologies existed, natural products were typically obtained either from plant extracts or from total chemical synthesis of the desired compound. In the case of some compounds, purification from natural sources can be problematic due to the need to resolve complex mixtures of closely related compounds, and our current best methods for chemical synthesis are limited by low yield and low specificity requiring additional painstaking purification. As an alternative approach, metabolic engineering allows biosynthetic pathways to be reconstructed in model organisms (typically microbiological hosts such as Escherichia coli) so that useful quantities of the desired product can be harvested.  In one example of this approach, Brazier-Hicks and Edwards developed a method for efficient production of C-glycosylated flavanoids for dietary studies by using gene synthesis to re-engineer a metabolic circuit in yeast. They designed synthetic variants of five genes that comprise the flavone-C-glycoside pathway in rice plants, which were subsequently codon-optimized for expression in yeast. These synthetic genes were used to construct a polyprotein cassette that expresses the entire metabolic circuit in a single step.

Sustainable energy from unconventional sources. While most efforts to develop biofuels have focused on carbohydrates and related compounds, Dellomonaco et al. showed that fatty acids can serve as biomass for sustainably produced biofuels by using gene synthesis to engineer several native and heterologous fermentative pathways to function in E.coli under aerobic conditions. These synthetically engineered bacteria convert fatty acid-rich feedstocks into desirable biofuels (ethanol and butanol) and biochemicals (acetate, acetone, isopropanol, succinate, and propionate), with higher yield than more widely used lignocellulosic sugars.