CrossRef enabled

PAC Archives

Archive →

Pure Appl. Chem., 2012, Vol. 84, No. 6, pp. 1407-1420

Published online 2011-12-08

Systematic isolation of microbial metabolites for natural products depository (NPDepo)

Hiroyuki Osada* and Toshihiko Nogawa

Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, Saitama 351-0198, Japan

Abstract: 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 β-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.