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Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity

Applied Microbiology and Biotechnology volume 100, pages 8349–8357 (2016)Cite this article

Abstract

The biotransformation of tanshinone IIA to a new antibacterial agent tanshisorbicin (1) by the fungus Hypocrea sp. (AS 3.17108) is described. The structure of tanshisorbicin is a hybrid of tanshinone IIA (2) and sorbicillinol (3). The latter is a metabolite produced by Hypocrea sp. The structure of tanshisorbicin was determined using mass spectrometry, NMR spectroscopy, and ECD calculations. The anti-MRSA activity of 1 was found to be significantly higher than that of the parent substrate Tan IIA. Preliminary experiments indicate that tanshisorbicin is formed via a [4+2] cycloaddition reaction that is likely catalyzed by microbial enzyme.

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Acknowledgments

This work was supported by the National Program on Key Basic Research Project (973 program, 2013CB734000) and by grants from the China Ocean Mineral Resources R&D Association (DY125-15-T-07), the National Natural Science Foundation of China (81573341, 81102369, 81302678, 31430002, 31400090, 31320103911, 31125002), the Ministry of Science and Technology of China (2013ZX10005004-005 and 2011ZX09102-011-11), the National Institutes of Health (GM40541), the Welch Foundation (F-1511), and the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 312184. L.Z. is an awardee of the National Distinguished Young Scholar Program in China.

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Authors and Affiliations

  1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Wenni He, Miaomiao Liu, Jingyu Zhang, Jianying Han, Huanqin Dai, Lixin Zhang & Xueting Liu

  2. Soil and Fertilizer Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu, 610066, China

    Xiaolin Li

  3. Department of Microbiology, College of Resource and Environment, Sichuan Agricultural University, Chengdu, 611130, China

    Xiaoping Zhang

  4. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia

    Wael M. Abdel-Mageed

  5. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Wael M. Abdel-Mageed

  6. Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Li Li

  7. State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

    Wenzhao Wang

  8. Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA

    Hung-wen Liu

  9. Department of Natural Products, China Pharmaceutical University, Nanjing, 210009, China

    Houwei Luo

  10. University of Chinese Academy of Sciences, Beijing, 100049, China

    Miaomiao Liu & Jianying Han

  11. Eskitis Institute, Griffith University, QLD, Brisbane, 4111, Australia

    Miaomiao Liu & Ronald J. Quinn

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  1. Wenni He
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He, W., Liu, M., Li, X. et al. Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity. Appl Microbiol Biotechnol 100, 8349–8357 (2016). https://doi.org/10.1007/s00253-016-7488-6

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  • DOI: https://doi.org/10.1007/s00253-016-7488-6

Keywords

  • Biotransformation
  • [4+2] cycloaddition reaction
  • Tanshinone IIA
  • Hypocrea sp