FIG 11.

Model of the regulatory network formed by the four regulatory proteins, FscR1 to FscR4, controlling production of the polyene antibiotic candicidin in Streptomyces sp. FR-008. FscR2 and FscR3 are located at the upper level of the network; FscR3 positively regulates fscR2, but FscR2 negatively regulates fscR3, forming a negative feedback loop. The two cross-regulating factors FscR1 and FscR4 are at the lower levels of the regulatory hierarchy, with fscR1 positively regulated by both FscR2 and FscR3 and fscR4 regulated positively by FscR2 but negatively by FscR3. FscR1 mediates the regulatory effect of the other three regulatory factors by directly regulating the structural genes. +, positive regulatory effect; −, negative regulatory effect. A red arrow indicates functional substitution of the upstream gene by the downstream gene, i.e., by the gene at the lower level of the hierarchy. *, locations of FscRI recognition sites in the promoters of the structural genes.