4-Hydroxybenzoic acid is a diffusible factor that connects metabolic shikimate pathway to the biosynthesis of a unique antifungal metabolite in Lysobacter enzymogenes

Zhenhe Su, Hongfu Chen, Ping Wang, Simon Tombosa, Liangcheng Du, Yong Han, Yuemao Shen, Guoliang Qian, Fengquan Liu

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Heat-stable antifungal factor (HSAF) produced by Lysobacter enzymogenes is a potential lead compound for developing new antibiotics. Yet, how L. enzymogenes regulates the HSAF biosynthesis remains largely unknown. Here, we show that 4-hydroxybenzoic acid (4-HBA) serves as a diffusible factor for regulating HSAF biosynthesis. The biosynthesis of 4-HBA involved an oxygenase, LenB2, and mutation of lenB2 almost completely abolished 4-HBA production, leading to significantly impaired HSAF production. Introduction of a heterologous gene coding for 4-HBA biosynthetic enzyme into the lenB2 mutant restored the production of 4-HBA and HSAF to their corresponding wild-type levels. Exogenous addition of 0.5–1 μM 4-HBA was sufficient to restore HSAF production in the lenB2 mutant. Furthermore, the shikimate pathway was found to regulate the biosynthesis of HSAF via 4-HBA. Finally, we identified a LysR-family transcription factor (LysRLe) with activity directed to HSAF production. LysRLe could bind to the HSAF promoter and, as a result, regulates expression of HSAF biosynthesis genes. The 4-HBA could bind to LysRLe and appeared to partly enhance formation of the LysRLe–DNA complex. Collectively, our findings suggest that L. enzymogenes produces 4-HBA to serve as an adaptor molecule to link the shikimate pathway to the biosynthesis of a unique antifungal metabolite (HSAF).

Original languageEnglish (US)
Pages (from-to)163-178
Number of pages16
JournalMolecular Microbiology
Volume104
Issue number1
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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