The starting strain was treated by ultraviolet irradiation,then it was screened further by laser compound mutation and studied on the genetic stability to obtain the stable high-yield nosiheptide-producing strains.The result showed that the potency of strain NXT-U19 was increased by 44.22% compared to the original strain(546.17 μg/mL),reaching 787.71 μg/mL.Six high-yield strains was screened by laser-ultraviolet compound mutation,among them the highest potency of strain NXT-U19-J2 was increased by 65.74% compared to the original strain,reaching 905.22 μg/mL.The analysis of subculture proved that the genetic stability of mutated strain NXT-U19-J2 was good.This result has showed that laser compound mutation is the efficient method to obtain the high-yield nosiheptide-producing strains.