Journal
PURE AND APPLIED CHEMISTRY
Volume 84, Issue 6, Pages 1407-1420Publisher
INT UNION PURE APPLIED CHEMISTRY
DOI: 10.1351/PAC-CON-11-08-11
Keywords
biosynthesis; fraction library; mass spectrometry; microbial products; MP plot; natural products; spectral database; systematic isolation; UV-vis spectroscopy
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A microbial fraction library has been constructed as a part of RIKEN Natural Products Depository (NPDepo) to discover and isolate novel metabolites with unique biological activity from microbial sources efficiently and rapidly. The fraction library was made by a systematic separation method based on basic chromatographic techniques. Each fraction in the library was analyzed by liquid chromatography/mass spectrometry (LC/MS) to reveal physicochemical properties of each metabolite within the fraction, and the results were applied to construct a database for rapid discovery of novel and structurally unique compounds. We developed a new type of metabolite database called MP (microbial products) plot to visualize each metabolite on a 2D area. The combination of the fraction library and the database led to the discovery and isolation of novel metabolites, verticilactam, which was a 16-membered macrolactam with an unprecedented beta-keto-amide moiety, and spirotoamides A and B, which had a highly substituted 6,6-spiroaccetal moiety and a carboxamide moiety. Moreover, based on the utilization of the MP plot, the new capacity of a streptomycete to produce specific metabolites was discovered.
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