Applied Microbiology and Biotechnology

, Volume 103, Issue 13, pp 5167–5181 | Cite as

Genome- and MS-based mining of antibacterial chlorinated chromones and xanthones from the phytopathogenic fungus Bipolaris sorokiniana strain 11134

  • Jianying Han
  • Jingyu Zhang
  • Zhijun Song
  • Miaomiao Liu
  • Jiansen Hu
  • Chengjian Hou
  • Guoliang Zhu
  • Lan Jiang
  • Xuekui Xia
  • Ronald J. Quinn
  • Yunjiang Feng
  • Lixin ZhangEmail author
  • Tom HsiangEmail author
  • Xueting LiuEmail author
Biotechnological products and process engineering


Halogen substituents are important for biological activity in many compounds. Genome-based mining of halogenase along with its biosynthetic gene cluster provided an efficient approach for the discovery of naturally occurring organohalogen compounds. Analysis of the genome sequence of a phytopathogenic fungus Bipolaris sorokiniana 11134 revealed a polyketide gene cluster adjacent to a flavin-dependent halogenase capable of encoding halogenated polyketides, which are rarely reported in phytopathogenic fungi. Furthermore, MS- and UV-guided isolation and purification led to the identification of five chlorine-containing natural products together with seven other chromones and xanthones. Two of the chlorinated compounds and four chromones are new compounds. Their structures were elucidated by NMR spectroscopic analysis and HRESIMS data. The biosynthetic gene clusters of isolated compounds and their putative biosynthetic pathway are also proposed. One new chlorinated compound showed activity against Staphylococcus aureus, methicillin-resistant S. aureus, and three clinical-resistant S. aureus strains with a shared minimum inhibitory concentration (MIC) of 12.5 μg/mL. Genome-based mining of halogenases combined with high-resolution MS- and UV-guided identification provides an efficient approach to discover new halogenated natural products from microorganisms.


Genome-based mining Halogenase Phytopathogenic fungus Bipolaris sorokiniana Antibacterial activity 


Funding information

This work was supported by grants from the National Natural Science Foundation of China (31430002, 81573341, 21877038, 31720103901, 31320103911), Open Project Funding of the State Key Laboratory of Bioreactor Engineering, the 111 Project (B18022), the Fundamental Research Funds for the Central Universities (22221818014), the Natural Science Foundation from Shandong Province (No. ZR2017ZB0206), and Taishan Scholarship. The authors acknowledge the Australian Research Council (ARC) for support (LE140100119, LE20100170). J. Han thanks the Griffith University for the provision of the Ph.D. scholarships (GUPRS and GUIPRS). Genome sequencing and assembly of BS11134 were supported by funding from the Natural Science and Engineering Research Council of Canada to T. Hsiang.

Compliance with ethical standards

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

253_2019_9821_MOESM1_ESM.pdf (2.2 mb)
ESM 1 (PDF 2207 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  2. 2.Griffith Institute for Drug DiscoveryGriffith UniversityBrisbaneAustralia
  3. 3.University of Chinese Academy of SciencesBeijingChina
  4. 4.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
  5. 5.Key Biosensor Laboratory of Shandong Province, Biology InstituteQilu University of Technology (Shandong Academy of Sciences)JinanChina
  6. 6.School of Environmental SciencesUniversity of GuelphGuelphCanada

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