FK506 (tacrolimus) is a clinically important immunosuppressant, produced in industrial fermentation processes by various Streptomyces species. Yields of FK506 in these processes remain relatively low and their efficiency is further reduced by the presence of structurally similar impurities in fermentation broths. Biosynthetic processes of secondary metabolites are often affected by regulatory genes, located in biosynthetic gene clusters. In this article we describe the identification and characterization of two regulatory elements present in the FK506 biosynthetic gene cluster fkbR and fkbN, belonging to the LysR and LAL family, respectively. Inactivation of these genes caused a dramatic reduction in FK506 yield whereas their overexpression significantly improved the yield of this compound. The results show a promising potential of the obtained genetically modified strains of to improve the yield of FK506 as well as FK506 analogues which are being produced in the scope of this project in S. tsukubaensis by chemobiosynthetic approach.
COBISS.SI-ID: 4146808