Lrp Family Regulator SCAB_Lrp2 Responds to the Precursor Tryptophan and Represses the Thaxtomin Biosynthesis in <i>Streptomyces scabies</i>

Streptomyces scabies is a well-researched plant pathogen belonging to the genus Streptomyces. Its virulence is linked to the production of the secondary metabolite thaxtomin A, which is tightly regulated at the transcriptional level. The leucine-responsive regulatory protein (Lrp) family is conserved in prokaryotes and is involved in various crucial biological processes. However, the regulatory interaction between Lrp protein and pathogenic Streptomyces species remains poorly understood. This study aims to explore the role of SCAB_Lrp2 in regulating thaxtomin biosynthesis and pathogenicity, and to analyse the shared and unique features of Lrp homologues in S. scabies. We observed that SCAB_Lrp2 (SCAB_75421) showed significant homology with SCAB_Lrp, a recognised activator of thaxtomin A production in S. scabies. Our results revealed a regulatory interaction between SCAB_Lrp2 and SCAB_Lrp in terms of their targets, although SCAB_Lrp2 does not respond to the amino acid-effectors of SCAB_Lrp. In contrast to SCAB_Lrp, deletion of SCAB_Lrp2 resulted in a notable increase in thaxtomin A production with the emergence of a hypervirulent phenotype in S. scabies. Further analysis revealed that SCAB_Lrp2 represses the transcription of the thaxtomin biosynthetic gene cluster by directly regulating the cluster-situated regulator (CSR) gene txtR. Moreover, the precursor of thaxtomin, tryptophan, acts as an effector of SCAB_Lrp2, strengthening the repressive effect on thaxtomin biosynthesis through txtR. These findings provide new insights into the functional conservation and diversity of Lrp homologues involved in the biosynthesis of thaxtomin phytotoxins in pathogenic Streptomyces species.