title: New on-line separation workflow of microbial metabolites via hyphenation of analytical and preparative comprehensive two-dimensional liquid chromatography.
abstract: Microbial metabolites represent an important source of bioactive natural products, but always exhibit diverse of chemical structures or complicated chemical composition with low active ingredients content. Traditional separation methods rely mainly on off-line combination of open-column chromatography and preparative high performance liquid chromatography (HPLC). However, the multi-step and prolonged separation procedure might lead to exposure to oxygen and structural transformation of metabolites. In the present work, a new two-dimensional separation workflow for fast isolation and analysis of microbial metabolites from Chaetomium globosum SNSHI-5, a cytotoxic fungus derived from extreme environment. The advantage of this analytical comprehensive two-dimensional liquid chromatography (2D-LC) lies on its ability to analyze the composition of the metabolites, and to optimize the separation conditions for the preparative 2D-LC. Furthermore, gram scale preparative 2D-LC separation of the crude fungus extract could be performed on a medium-pressure liquid chromatograph×preparative high-performance liquid chromatography system, under the optimized condition. Interestingly, 12 cytochalasan derivatives, including two new compounds named cytoglobosin Ab (3) and isochaetoglobosin Db (8), were successfully obtained with high purity in a short period of time. The structures of the isolated metabolites were comprehensively characterized by HR ESI-MS and NMR. To be highlighted, this is the first report on the combination of analytical and preparative 2D-LC for the separation of microbial metabolites. The new workflow exhibited apparent advantages in separation efficiency and sample treatment capacity compared with conventional methods.
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
authors: Xia
authors: X
authors: Yan
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
authors: Li-Juan
authors: LJ
authors: Wang
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
authors: Zhen
authors: Z
authors: Wu
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
authors: Yun-Long
authors: YL
authors: Wu
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
authors: Xiu-Xiu
authors: XX
authors: Liu
authors: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, China.
authors: Fang-Rong
authors: FR
authors: Chang
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China. Electronic address: fangmj@xmu.edu.cn.
authors: Mei-Juan
authors: MJ
authors: Fang
authors: Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China. Electronic address: qyk@xmu.edu.cn.
authors: Ying-Kun
authors: YK
authors: Qiu
mesh_terms: D002597:Chaetomium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003572:Cytochalasins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D008956:Models, Chemical
chemical_list: D003572:Cytochalasins
keywords: Chaetomium globosum SNSHI-5; Comprehensive two dimensional liquid chromatography; Cytochalasan derivatives; Medium-pressure liquid chromatograph×preparative high-performance liquid chromatography