원문정보
초록
영어
FK506(Tacrolimus) produced by various Streptomyces species is an important 23-membered polyketide macrolide effecting on immunosuppression. Recently, the sequences of the entire FK506 biosynthetic gene clusters from Streptomyces sp. strain KCTC 11604BP was reported and analyzed. One of the putative regulatory genes, fkbN gene encoded an LAL(large ATP-binding regulators of LuxR) family regulator. However, the function of this putative regulatory gene, founds in the FK506 biosynthetic gene clusters has not been reported. This study show that the identical function of fkbN in the regulation of FK506 biosynthesis in Streptomyces sp. KCTC 11604BP through the overexpression, in-frame deletion, complementation of fkbN deletion mutants, and transcriptional analysis of FK506 biosynthetic genes by semiquantitative reverse transcription-PCR(RT-PCR) in the wild-type and mutant strains. fkbN overexpression improved the levels of FK506 production by approximately 2.0-fold, and a deletion of fkbN caused the complete loss of FK506 production. These results suggest that fkbN plays a key role as a positive regulator of the FK506 biosynthetic pathway and demonstrate the potential of manipulating regulatory genes to increase the level of FK506 production in industrial production strains.