Tuesday, July 28, 2009 - 4:00 PM
S91
Production of microbial natural products by mixed-phase fermentation: combined liquid-solid approaches
Ramunas Bigelis, Deborah M. Roll, Hui Y. Yang, and Haiyin He. Natural Products Discovery Research, Chemical Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965
New fermentation technologies for microbial natural products complement bioprospecting projects for previously unknown compounds, and offer new approaches for pharmaceutical discovery programs. Mixed phase fermentation (MPF), a combined liquid-solid approach, bridges liquid phase fermentation (LPF) and solid phase fermentation (SPF), and facilitates the discovery of new natural products. MPF employs inert solid supports in abundant liquid, increases surface area available for growth (at times simulating the microarchitecture of natural habitats), exploits the tendency of some microorganisms to adhere to solid surfaces, and influences differentiation and developmental programs that are linked to secondary metabolism in fungi and actinomycetes. Three different support configurations during MPF serve as examples of this fermentation approach: (i) stationary supports on agar surfaces, (ii) agitated supports in liquid medium, and (iii) stationary supports bearing abundant liquid and dispersed milled cereal grains or processed solid substrates. MPF has facilitated the discovery of new compounds such as the pyrrocidines and acremonidins from fungi, and also enhanced the production of known microbial natural products. MPF with diverse filamentous fungi and actinomycetes in agitated shake-flasks bearing a polymeric support consistently influenced morphology, growth, and mycelial immobilization -- and sometimes the production of bioactive secondary metabolites. LCMS analysis of MPF extracts revealed elevated levels of specific metabolites compared to extracts obtained by LPF. MPF provides new avenues for natural product discovery with known and unique isolates, as well as offering insights into cell density-dependent group behavior of actinomycetes and fungi.
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See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)