title: High-throughput profiling of microbial extracts.
abstract: Microbial culture extracts are used for natural products screening in the drug lead discovery process. An extract of a microbial culture is a complex mixture of organic compounds, making it difficult to evaluate the diversity and redundancy of the compounds. However, having a diverse extract library is a key to success in generating a lead for drug discovery. We have developed a high-throughput and robust LC-MS analysis and data processing method for visualizing sample profile and diversity. In the LC-MS analysis of 16 025 microbial culture extracts, positive and negative ions were acquired simultaneously with an electrospray ionization source. The raw data were processed using ACD IntelliXtract, and peak lists of each extract were generated and stored in the database. The peak list data were binned by nominal mass (m/z 150-1350) and retention time. How frequently the binned peaks, termed peak identifiers, appeared in the extracts library was calculated, and these data were visualized by scattered plots in Spotfire. From 4 to 115 peaks were observed in each sample. As it is easy to eliminate the ubiquitous peaks shown in most samples and simplify the plots, the unique or redundant compounds could be detected.
authors.affiliation: Discovery Science & Technology Department, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530 Japan. itotty@chugai-pharm.co.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Takamichi
authors.initials: T
authors.lastname: Odake
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Katoh
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoki
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods; D055808:Drug Discovery; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D001688:Biological Products; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries