Prenyltransferases play important roles in the diversification of natural products and the improvement of biological activities. A UbiA-type prenyltransferase CdnC with substrate promiscuity was identified as the pivotal builder of the noncanonical chrodrimanin skeletons, which carry a benzo-cyclohexanone structure as the nonterpene part. In vitro and heterologous expression studies with CdnC led to the production of a series of novel chrodrimanin-like structures. The discovery of CdnC offers a referable strategy for the biosynthesis and structural diversification of farnesyl-derived meroterpenoids.