There is an increasing need for biorenewables alternatives to fossil fuel-derived products. This demand has created an opportunity for constructing biosynthetic routes to natural products, including polyketides. We have engineered a type III polyketide synthase (Gerbera hybrida 2-pyrone synthase) and the yeast host Saccharomyces cerevisiae for the in vivo synthesis of triacetic acid lactone (TAL). This platform chemical is useful for downstream conversion to a variety of products including the common food preservative, sorbic acid. Enzyme engineering was performed to identify robust biocatalysts with improved stability and activity, yielding 3-fold increases in specific TAL production over the wildtype synthase. The pathways in the yeast host have been engineered for increased precursor and cofactor pools, leading to 3-fold increases relative to the base strain. A combination of the promising synthase variants, the engineered strains, and improved expression conditions resulted in TAL titers of over 1.7 g/L, and a yield of 0.17 g/g glucose (37% of the theoretical yield). These approaches should be directly applicable to the synthesis of other polyketide products.

Engineering Gerbera hybrida 2-pyrone synthase (2-PS) and host Saccharomyces cerevisiae? for the high-level synthesis of triacetic acid lactone

247th National Meeting (2014)

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