title: Fungal biotransformation of tanshinone results in [4+2] cycloaddition with sorbicillinol: evidence for enzyme catalysis and increased antibacterial activity.
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.
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Wenni
authors.initials: W
authors.lastname: He
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.|Eskitis Institute, Griffith University, QLD, Brisbane, 4111, Australia.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Soil and Fertilizer Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu, 610066, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Microbiology, College of Resource and Environment, Sichuan Agricultural University, Chengdu, 611130, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 11451, Kingdom of Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt.
authors.forename: Wael M
authors.initials: WM
authors.lastname: Abdel-Mageed
authors.affiliation: Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenzhao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Han
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Huanqin
authors.initials: H
authors.lastname: Dai
authors.affiliation: Eskitis Institute, Griffith University, QLD, Brisbane, 4111, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry, University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Natural Products, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Houwei
authors.initials: H
authors.lastname: Luo
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. zhanglixin@im.ac.cn.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. liuxt2010@gmail.com.
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D061565:Cycloaddition Reaction; D003512:Cyclohexanones / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D014242:Trichoderma / Q000378:metabolism*
chemical_list: D045784:Abietanes; D000890:Anti-Infective Agents; D003512:Cyclohexanones; C453419:sorbicillinol; C021751:tanshinone
keywords: Biotransformation; Hypocrea sp; Tanshinone IIA; [4+2] cycloaddition reaction