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There exist up to seven regulatory genes in the pristinamycin biosynthetic cluster of Streptomyces pristinaespiralis,which infers a complicated regulation mechanism for pristinamycin production.In this study,we revealed that PapR6,a putative atypical response regulator,acts as a pathway-specific activator of pristinamycin Ⅱ (PⅡ) biosynthesis.Deletion of the papR6 gene resulted in a significantly reduced PⅡ production and its overexpression led to a higher PⅡ formation comparing with the parental strain HCCB 10218.However,either papR6 deletion or overexpression has very little effect on pristinamycin Ⅰ (PI) biosynthesis.