English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Because of the remarkable efficacy in treating  mycobacterial  infections, rifamycin and its derivatives are still first-line antimycobacterial drugs. It has been intensely studied to increase rifamycin yield from  Amycolatopsis mediterranei , and nitrate is found to provide a stable and remarkable stimulating effect on the rifamycin production, a phenomenon known as “nitrate-stimulating effect (NSE)”. Although the NSE has been widely used for the industrial production of rifamycin, its detailed molecular mechanism remains ill-defined. And our previous study has established that the global nitrogen regulator GlnR may participate in the NSE, but the underlying mechanism is still enigmatic. Here, we demonstrate that GlnR directly controls rifamycin biosynthesis in  A. mediterranei  and thus plays an essential role in the NSE. Firstly, GlnR specifically binds to the upstream region of  rifZ , which leads us to uncover that  rifZ  has its own promoter. As RifZ is a pathway-specific activator for the whole  rif  cluster, GlnR indirectly upregulates the whole  rif  cluster transcription by directly activating the  rifZ  expression. Secondly, GlnR specifically binds to the upstream region of  rifK , which is also characterized to have its own promoter. It is well-known that RifK is a 3-amino-5-hydroxybenzoic acid (AHBA, the starter unit of rifamycin) synthase, thus GlnR can promote the supply of the rifamycin precursor by directly activating the  rifK  transcription. Notably, GlnR and RifZ independently activate the  rifK  transcription through binding to different sites in  rifK  promoter region, which suggests that the cells have a sophisticated regulatory mechanism to control the AHBA biosynthesis. Collectively, this study reveals that GlnR activates the  rif  cluster transcription in both direct (for  rifZ  and  rifK ) and indirect (for the whole  rif  cluster) manners, which well interprets the phenomenon that the NSE doesn’t occur in the  glnR  null mutant. Furthermore, this study deepens our understanding about the molecular mechanism of the NSE.

GlnR Dominates Rifamycin Biosynthesis by Activating the rif Cluster Genes Transcription Both Directly and Indirectly in Amycolatopsis mediterranei