Biologically active cannabinoids are derived from cannabigerolic acid (CBGA), which is biosynthesized by aromatic prenyltransferase CsPT4. We exploit the catalytic versatility of CsPT4 to synthesize various CBGA analogues, including a geranylated bibenzyl acid, the precursor to bibenzyl cannabinoids of liverwort origin. The synthesized natural and new-to-nature cannabinoids exhibit potent cytotoxicity in human pancreatic cancer cells. CsPT4 can artificially extend the cannabinoid biosynthetic diversity with novel and improved biological activities.