Abstract:[Objective] Streptomyces is a genus of Gram-positive aerobic bacteria characterized by complex morphological differentiation and potent secondary metabolite-producing ability. SapB, a class III lanthipeptide, promotes the morphological differentiation of Streptomyces coelicolor, which suggests that SapB-like peptides might be developed as targets for engineering of morphological differentiation. In this study, we characterized the effects of SapB-like peptides on the morphological differentiation of multiple Streptomyces species, aiming to provide a theoretical basis for the engineering of these peptides. [Methods] Bioinformatics tools were used to analyze the gene clusters for the synthesis of SapB-like peptides in the genomes of Streptomyces spp.. The plasmids for heterologous expression were constructed and introduced into Streptomyces spp. through conjugation. The colony and mycelial morphology were compared to reveal the effects of these peptides on the morphological differentiation of Streptomyces. [Results] SapB-like peptides promoted the differentiation of Streptomyces from vegetative to aerial mycelia. Specifically, they increased the aerial mycelia and accelerated the differentiation, thus shortening the morphological differentiation cycle. [Conclusion] SapB-like peptides can help shorten the morphological differentiation cycle of Streptomyces, demonstrating the potential for the morphological differentiation engineering of Streptomyces.