SACE_Lrp negatively regulates erythromycin production in Saccharopolyspora erythraea. SACE_Lrp directly regulates the BCAA transport and indirectly regulates the BCAA catabolism in S. erythraea. SACE_Lrp is the first reported Lrp showing two-directional response to its amino acid-effectors. A high erythromycin-producing strain has been constructed by engineering the SACE_Lrp regulatory elements.