Whole-cell biocatalysts have gained increased interest as a method for producing chemicals and fuels renewably due to concerns over future fossil fuel supplies. Utilizing microorganisms as a catalyst offers several advantages over conventional synthesis: high enantioselectivity and regioselectivity, are self-replicating and self-maintaining, and can achieve high multistep efficiency from a single renewable carbon source. Biosynthesis of various fuels and bulk chemicals has been demonstrated in microbial hosts such as Escherichia coli. A lesser-explored advantage of whole-cell biocatalysis is the ability to achieve multi-part syntheses, whereby multiple products must be generated in parallel within the same vessel and further combined into a final product. Whole-cell biocatalysis can potentially perform such a multi-part synthesis efficiently in one vessel. Another significant advantage of utilizing a bacterial system is the ability to catalyze reactions under ambient temperatures and in aqueous solution. Here we explore the potential of multi-part synthesis in E. coli.  We engineered E. coli to expand natural metabolism and produce several target chemicals specifically and efficiently through systematic comparison of components in each step of the biosynthetic pathway and careful matching of genes, pathway, and chemical toxicity to the chosen host.

Systematic construction of biosynthetic pathways for fuel molecules

247th National Meeting (2014)

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