FKS06 is the clinically important 23-membered macrocyclic immunosuppressive polyketide produced by a variety of Streptomyces species [1,2].To investigate the biosynthesis of FK506.the entire biosynthetic gene clusters of FKS06 from three different strains were isolated and sequenced.Genes encoding the polyketide synthases (PKSs) (fKbB,fkbC and fkbA),the lysine cyclodeaminase (fkbL).the peptide synthetase (fkbP).the 31-O-methyltransferase (fkbM),the C-9hydroxylaseoxidase (fkbD).