Enzymes of Type III polyketide synthase superfamily play an important role in the biosynthesis of medicinal natural products in plants. The PKSs generate the diversity of polyketide derivatives by changing their preference for starter molecules, the number of acetyl additions catalysed and the cyclisation of the polyketide intermediates. The amazing structural features of gingerol and related compounds of ginger (Zingiber officinale Rosc., Zingiberaceae) provide a genomic insight in to the presence of novel forms of PKS. The current study describes the isolation and characterisation of a novel of PKS from Z. officinale using degenerate oligonucleotide based PCR method. The inducible expression of recombinant ZoPKS in E. coli resulted in the formation of a protein with approximate molecular weight of 43kD. The comparative sequence and phylogenetic analysis of ZoPKS shows its significant variation from already identified PKSs. The novelty of the ZoPKS was further confirmed by homology modeling based comparative structural bioinformatics analysis. The novel form of PKS identified in the study has very remarkable amino acid substitutions at the key residues determining the starter substrate selectivity and condensation reactions and forms a genomic basis of PKS from Z. officinale to explore its potential in biosynthesis of gingerol and related compounds.