S100: An integrated strategy for generating fatty acid-based biorenewable chemicals: Diversifying fatty acid synthesis with polyketide synthesis biocatalysts

The chemical industry is primarily reliant on inexpensive, petroleum-based carbon feedstocks that generate a small collection of platform-chemicals, from which a large collage of chemical products is produced.  Given this paradigm, the Center for Biorenewable Chemicals is exploring the potential of exploiting the polyketide/fatty acid biosynthetic pathways as a target metabolic process that can be bioengineered for the production of platform-biorenewable chemicals.  Polyketide and fatty acid biosynthesis share a common series of biocatalytic mechanisms that reiteratively generate a homologous series of alkyl-chains that are between 4-carbon atoms to greater than 30-carbon atoms in chain length.  These metabolic processes share the common chemistry of containing alternating carbonyl and methylene functional groups in their structures, and in the intermediates of their biosynthetic origins.  By amalgamating biocatalysts derived from diverse metabolic and phylogenetic origins within an integrated biological system, we are envisioning a single technological platform that could generate a variety of biorenewable molecules, which are of variable carbon-chain lengths, and carrying defined functional chemical groups at specific sites on the alkyl-chain.  Because the envisioned system is based on the reiteration of a series of simple transformations on a homologous series of substrates to generate a collection of chemical products, by analogy to combinatorial chemistry, the envisioned platform can be considered an example of combinatorial metabolism.  Initial research that will be discussed has two foci: 1) biocatalysts that can prematurely terminate the elongation process, and 2) biocatalysts that condense modified acyl-intermediates, resulting in the production of chemically functionalized products.