Biological systems have the potential to produce a wide array of compounds with uses that include fuels, materials, bulk chemicals, and pharmaceuticals.  Our group is focused on applying principles from metabolic engineering and biocatalysis towards the design and construction of novel biosynthetic pathways for specified target compounds.  This �retro-biosynthetic design� approach is aided by advancements in the development of new tools under the umbrella of synthetic biology that facilitate re-engineering of biological systems.  We have constructed a synthetic pathway for the production of glucaric acid, deemed a �top-value added chemical� from biomass, from glucose in Escherichia coli.  Co-expression of the genes encoding myo-inositol-1-phosphate synthase (Ino1) from Saccharomyces cerevisiae, myo-inositol oxygenase (MIOX) from mouse, and uronate dehydrogenase (Udh) from Pseudomonas syringae led to production of glucaric acid.  Flux towards glucaric acid is ultimately limited by MIOX, whose activity is greatly affected by the concentration of myo-inositol, its substrate, present while it is being expressed.  To improve glucaric acid production, we have explored several options for increasing flux through the pathway.  I will present results that show that the use of solubility partners significantly enhances the activity and stability of MIOX and suggest that new approaches for regulation of gene expression are required.  A new system for modulating glucose flux through host strain engineering, in order to enhance productivity, will also be introduced.

Microbial synthesis of glucaric acid: A case study for the design, assembly, and improvement of a biosynthetic pathway for value-added products

247th National Meeting (2014)

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