AUTHOR=Misaki Yuya , Yamamoto Shouji , Suzuki Toshihiro , Iwakuni Miyuki , Sasaki Hiroaki , Takahashi Yuzuru , Inada Kuninobu , Kinashi Haruyasu , Arakawa Kenji 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01089

DOI=10.3389/fmicb.2020.01089

ISSN=1664-302X

ABSTRACT=<p><italic>Streptomyces rochei</italic> 7434AN4, a producer of lankacidin (LC) and lankamycin (LM), carries many regulatory genes including a biosynthesis gene for signaling molecules SRBs (<italic>srrX</italic>), an SRB receptor gene (<italic>srrA</italic>), and a SARP (<italic>Streptomyces</italic> antibiotic regulatory protein) family activator gene (<italic>srrY</italic>). Our previous study revealed that the main regulatory cascade goes from <italic>srrX</italic> through <italic>srrA</italic> to <italic>srrY</italic>, leading to LC production, whereas <italic>srrY</italic> further regulates a second SARP gene <italic>srrZ</italic> to synthesize LM. In this study we extensively investigated the function of <italic>srrB</italic>, a pseudo-receptor gene, by analyzing antibiotic production and transcription. Metabolite analysis showed that the <italic>srrB</italic> mutation increased both LC and LM production over four-folds. Transcription, gel shift, and DNase I footprinting experiments revealed that <italic>srrB</italic> and <italic>srrY</italic> are expressed under the SRB/SrrA regulatory system, and at the later stage, SrrB represses <italic>srrY</italic> expression by binding to the promoter region of <italic>srrY</italic>. These findings confirmed that SrrB acts as a negative regulator of the activator gene <italic>srrY</italic> to control LC and LM production at the later stage of fermentation in <italic>S. rochei</italic>.</p>