SrrB, a Pseudo-Receptor Protein, Acts as a Negative Regulator for Lankacidin and Lankamycin Production in Streptomyces rochei .

Streptomyces rochei7434AN4, a producer of lankacidin (LC) and lankamycin (LM), carries many regulatory genes including a biosynthesis gene for signaling molecules SRBs (srrX), an SRB receptor gene (srrA), and a SARP (Streptomycesantibiotic regulatory protein) family activator gene (srrY). Our previous study revealed that the main regulatory cascade goes fromsrrXthroughsrrAtosrrY, leading to LC production, whereassrrYfurther regulates a second SARP genesrrZto synthesize LM. In this study we extensively investigated the function ofsrrB, a pseudo-receptor gene, by analyzing antibiotic production and transcription. Metabolite analysis showed that thesrrBmutation increased both LC and LM production over four-folds. Transcription, gel shift, and DNase I footprinting experiments revealed thatsrrBandsrrYare expressed under the SRB/SrrA regulatory system, and at the later stage, SrrB repressessrrYexpression by binding to the promoter region ofsrrY. These findings confirmed that SrrB acts as a negative regulator of the activator genesrrYto control LC and LM production at the later stage of fermentation inS. rochei.