Monday, July 30, 2007
P68

New approaches to natural product discovery: mixed-phase fermentation for secondary metabolites from actinomycetes and fungi

Ramunas Bigelis1, Haiyin He2, Hui Y. Yang2, Scott W. Luckman1, Li-Ping Chang1, and Deborah M. Roll1. (1) Natural Products Discovery Research, Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, (2) Natural Products Discovery Research, Chemical Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965

Mixed-phase fermentation (MPF), fermentation with a solid support in abundant liquid medium, influences actinomycete and fungal secondary metabolism and adds to the value of these microorganisms as sources of natural products and potential therapeutic compounds.  Collections of diverse filamentous fungi and actinomycetes were grown by MPF in shake-flasks bearing polymeric supports.  The addition of a polyurethane support consistently influenced fungal growth, morphology, mycelial immobilization, and often the production of secondary metabolites in 2 media.  In a majority of cases, LCMS analysis revealed elevated levels of specific metabolites in methanol extracts obtained by MPF in comparison to extracts obtained by conventional shake-flask fermentation.  Similarly, the addition of a polyester-cellulose support consistently influenced the culture morphology of 184 unique actinomycetes fermented in 4 media.  Most actinomycetes were immobilized on the support resulting in a clear culture broth after agitation.  Concentrated actinomycete methanol extracts prepared after MPF were compared with those obtained after conventional fermentation to assess their bioactivities.  A higher percentage of MPF extracts showed antimicrobial activity against various antibiotic-resistant and antibiotic–susceptible test organisms, thus identifying more candidate actinomycete cultures for further screening.  MPF affords new avenues for natural product discovery and complements bioprospecting for new compounds from unique isolates, as well as providing insights into the sociomicrobiology of actinomycetes and fungi.

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