Fig. 6

Analysis of FK506 production, relative expression levels and genetic stability. a FK506 production at 168 h in strains by substitution of the bidirectional promoter region controlling the expression of both fkbN and tcs7. b Relative expression levels of selected genes in S. tsukubaensis L19-9 compared with L19-2. Excluding genes located in the FK506 biosynthetic gene cluster, genes residing upstream and downstream regions of the FK506 biosynthetic gene cluster were also included. c Production-stability of the high-yielding strain L19-9 in shake-flask culture. The strain was continuously cultured for 5 generations on ISP4 agar plates and the FK506 production was analyzed. Each experiment was repeated for three times and error bars showed standard deviations. The asterisks indicated the statistic significant differences. *P < 0.05; ****P < 0.0001; N, no significant difference