Described herein are non-natural variants of prenyltronsfcrases having at least one amino acid substitution as compared to its corresponding natural or unmodified prenyltransferascs. The variants are capable of an increased rate of formation of prenylated aromatic compounds, such as cannabinoids, as compared to a wild type control The prcnyltransferase variants can be expressed in an engineered microbe having a pathway to such cannabinoids, and optionally can include one or more other pathway transgencs to promote formation of substrate(s) for the prcnyltransferases. Therapeutically useful cannabinoids can be purified from engineered cells and cell cultures.