Cyclic di-GMP-Dependent Regulation of Antibiotic Biosynthesis in Lysobacter

  • Guoliang QianEmail author
  • Gaoge Xu
  • Shan-Ho Chou
  • Mark Gomelsky
  • Fengquan Liu


Lysobacter enzymogenes is an environmental bacterium that secrets a heat-stable antifungal factor, HSAF, an antibiotic against crop fungal pathogens. Elevated levels of cyclic di-GMP inhibit HSAF synthesis. The transcription factor cAMP receptor-like protein Clp binds to two sites upstream of the promoter of the HSAF biosynthesis operon and activates gene expression. At elevated cyclic di-GMP levels, cyclic di-GMP binding to Clp compromises binding to DNA, particularly at the low-affinity binding site, which results in lower expression of the HSAF biosynthesis operon. Two cyclic di-GMP phosphodiesterases contribute the most to cyclic di-GMP-dependent regulation of HSAF production. One of them, the GGDEF-EAL protein, LchP, forms a protein complex with Clp. Such specificity of targeted action allows LchP that has relatively weak phosphodiesterase activity, to play an oversized role in Clp-dependent HSAF biosynthesis. The HD-GYP phosphodiesterase RpfG is another major phosphodiesterase, whose activity is increased at higher cell density via a quorum-sensing mechanism. Further, a common regulator of type IV pilus synthesis, PilR, modulates HSAF biosynthesis via an as yet uncharacterized cyclic di-GMP signaling pathway. These findings represent novel insights into cyclic di-GMP-dependent antibiotic biosynthesis regulation in an agriculturally important bacterium.


Lysobacter Cyclic di-GMP Phosphodiesterase Diguanylate cyclase HSAF Cyclic di-GMP-binding receptor 



This study was supported by the Natural Science Foundation of Jiangsu Province (BK20190026; BK20181325 to GQ), the Fundamental Research Funds for the Central Universities (KJJQ202001; KYT201805 and KYTZ201403 to GQ), National Natural Science Foundation of China (31872016 and 31572046 to GQ) and National Basic Research (973) Program of China (2015CB150600 to GQ). Shan-Ho Chou was supported by the MoST grant of Taiwan (105-2113-M-005-013-MY2). Mark Gomelsky was supported by US National Institutes of Health (R21 AI135683-01).

Conflict of Interest Statement

None declared.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Guoliang Qian
    • 1
    • 2
    Email author
  • Gaoge Xu
    • 3
  • Shan-Ho Chou
    • 4
    • 6
  • Mark Gomelsky
    • 5
  • Fengquan Liu
    • 3
  1. 1.College of Plant ProtectionNanjing Agricultural UniversityNanjingChina
  2. 2.Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of EducationNanjing Agricultural UniversityNanjingPeople’s Republic of China
  3. 3.Institute of Plant Protection, Jiangsu Academy of Agricultural SciencesNanjingPeople’s Republic of China
  4. 4.Institute of Biochemistry and Agricultural Biotechnology CenterNational Chung Hsing UniversityTaichungTaiwan
  5. 5.Department of Molecular BiologyUniversity of WyomingLaramieUSA
  6. 6.State Key Laboratory of Agricultural Microbiology, College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanPeople’s Republic of China

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