Abstract: The present disclosure provides engineered variants of a cannabidiolic acid synthase (CBDAS) polypeptide comprising an amino acid sequence of SEQ ID NO:3 with one or more amino acid substitutions, nucleic acids comprising nucleotide sequences encoding said engineered variants, methods of making modified host cells comprising said nucleic acids, modified host cells expressing said engineered variants, methods of producing cannabinoids or cannabinoid derivatives, and methods of screening engineered variants of the cannabidiolic acid synthase (CBDAS) polypeptide.