Expanding the Chemical Palette of Industrial Microbes: Metabolic Engineering for Type III PKS-Derived Polyketides

Polyketides are a unique class of molecules with attractive bioactive and chemical properties. As a result, biorenewable production is being explored with these molecules as potential pharmaceutical, fuel, and material precursors. In particular, type III polyketide synthases enable access to a diverse class of chemicals using a relatively simple biochemical synthesis pathway. In this review, the recent advances in the engineering of microbial hosts for the production of type III PKS-derived polyketides are highlighted. In particular, the field has moved beyond simple proof-of-concept and has been exploring engineering efforts that have led to improved production scales. This review details engineering progress for the production of acetyl-CoA- and malonyl-CoA-derived polyketides including the products triacetic acid lactone and phloroglucinol as well as polyphenolic, phenylpropanoid-derived compounds including flavonoids, stilbenoids, and curcuminoids. Specifically, the authors focus on enumerating the metabolic engineering strategies employed and product titers achieved for these molecules. Finally, the authors highlight tools and strategies that can be leveraged to realize the potential of microbial production and diversification of these molecules.