Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation

Wenni He; Miaomiao Liu; Pei Huang; Wael M Abdel-Mageed; Jianying Han; Jeramie D Watrous; Don D Nguyen; Wenzhao Wang; Fuhang Song; Huanqin Dai; Jingyu Zhang; Ronald J Quinn; Tanja Grkovi; Houwei Luo; Lixin Zhang; Xueting Liu

doi:10.1016/j.synbio.2016.05.002

Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio-transformation

Synth Syst Biotechnol. 2016 Jul 1;1(3):187-194. doi: 10.1016/j.synbio.2016.05.002. eCollection 2016 Sep.

Authors

Wenni He¹, Miaomiao Liu^{1

2

3}, Pei Huang^{1

2}, Wael M Abdel-Mageed^{4

5}, Jianying Han^{1

2}, Jeramie D Watrous⁶, Don D Nguyen⁶, Wenzhao Wang⁷, Fuhang Song¹, Huanqin Dai¹, Jingyu Zhang¹, Ronald J Quinn³, Tanja Grkovi³, Houwei Luo⁸, Lixin Zhang¹, Xueting Liu¹

Affiliations

¹ Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
³ Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia.
⁴ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
⁵ Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
⁶ Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA 92093, United States.
⁷ State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁸ Department of Natural Products, China Pharmaceutical University, Nanjing 210009, China.

Abstract

Two potent anti-MRSA tanshinone glycosides (1 and 2) were discovered by targeted microbial biotransformation, along with rapid identification via MS/MS networking. Serial reactions including dehydrogenation, demethylations, reduction, glycosylation and methylation have been observed after incubation of tanshinone IIA and fungus Mucor rouxianus AS 3.3447. In addition, tanshinosides B (2) showed potent activities against serial clinical isolates of oxacillin-resistant Staphylococcus aureus with MIC values of 0.78 μg/mL. This is the first study that shows a significant increase in the level and activities of tanshinone glycosides relative to the substrate tanshinone IIA.

Keywords: Biotransformation; Glycosylation; Mucor rouxianus; Tanshinone IIA.