Thiopeptide antibiotics are an important class of natural products arising from posttranslational modifications of ribosomally synthesized peptides.As a member of this family.cyclothiazomycin possesses a unique bridged macrocyclic structure derived from an 18-aa structural peptide.Herein we reported the cloning,sequencing and a profile of heterologous expressions of the cyclothiazomycin biosynthetic gene cluster from Streptomyces hygroscopicus 10-22.Remarkably.the successful heterologous expression of a 22.7-kb gene cluster in S.lividans 1326 suggested a minimum set of 15 ORFs required for cyclothiazomycin production.