Paper: Discovery of novel cytotoxic metabolites from <i>Pseudomonas </i>sp. via co-culture and altered media conditions (2012 Annual Meeting and Exhibition (August 12-16, 2012))

Sunday, August 12, 2012

Columbia Hall, Terrace Level (Washington Hilton)

Suzanne M. Shipley¹, Terri DeLloyd¹, Min He², David J. Newman² and Karina M. Zuck¹, (1)Natural Products Support Group, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, (2)Natural Products Branch, Frederick National Laboratory for Cancer Research, Frederick, MD

Pseudomonas has a wide natural occurrence in soil, water, and plants, and is known to produce a broad array of bioactive secondary metabolites, including the analogs of spliceostatin A, FR901463, FR901464, and FR901465. Analysis of the genomic clusters of Pseudomonas indicate that it may be capable of producing many more natural products than the ones described to date. With the goal of isolating novel metabolites from Pseudomonas, we attempted to mimic its natural environment via co-culture. Growing Pseudomonas in the presence of another microorganism better represents a natural ecosystem where secondary metabolites are produced in an effort to compete and survive. Through co-culture and altering fermentation conditions, new analogs of spliceostatin A, exhibiting nanomolar GI₅₀ values in the NCI60 Tumor Cell Line screen, were derived. The fermentation conditions, structures and biological data will be presented. Funded by NCI Contract No. HHSN261200800001E.

P149: Discovery of novel cytotoxic metabolites from Pseudomonas sp. via co-culture and altered media conditions