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

Wenni He; Miaomiao Liu; Xiaolin Li; Xiaoping Zhang; Wael M Abdel-Mageed; Li Li; Wenzhao Wang; Jingyu Zhang; Jianying Han; Huanqin Dai; Ronald J Quinn; Hung-Wen Liu; Houwei Luo; Lixin Zhang; Xueting Liu

doi:10.1007/s00253-016-7488-6

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

Appl Microbiol Biotechnol. 2016 Oct;100(19):8349-57. doi: 10.1007/s00253-016-7488-6. Epub 2016 May 20.

Authors

Wenni He¹, Miaomiao Liu^{1

2

3}, Xiaolin Li⁴, Xiaoping Zhang⁵, Wael M Abdel-Mageed^{6

7}, Li Li⁸, Wenzhao Wang⁹, Jingyu Zhang¹, Jianying Han^{1

2}, Huanqin Dai¹, Ronald J Quinn³, Hung-Wen Liu¹⁰, Houwei Luo¹¹, Lixin Zhang¹², Xueting Liu¹³

Affiliations

¹ Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
² University of Chinese Academy of Sciences, Beijing, 100049, China.
³ Eskitis Institute, Griffith University, QLD, Brisbane, 4111, Australia.
⁴ Soil and Fertilizer Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu, 610066, China.
⁵ Department of Microbiology, College of Resource and Environment, Sichuan Agricultural University, Chengdu, 611130, China.
⁶ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
⁸ Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
⁹ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
¹⁰ Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
¹¹ Department of Natural Products, China Pharmaceutical University, Nanjing, 210009, China.
¹² Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].
¹³ Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].

PMID: 27198724
DOI: 10.1007/s00253-016-7488-6

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.

Keywords: Biotransformation; Hypocrea sp; Tanshinone IIA; [4+2] cycloaddition reaction.

MeSH terms

Abietanes / metabolism*
Anti-Infective Agents / chemistry
Anti-Infective Agents / metabolism*
Biotransformation
Cycloaddition Reaction
Cyclohexanones / chemistry
Cyclohexanones / metabolism*
Mass Spectrometry
Methicillin-Resistant Staphylococcus aureus / drug effects
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Trichoderma / metabolism*

Substances

Abietanes
Anti-Infective Agents
Cyclohexanones
sorbicillinol
tanshinone