Monday, July 30, 2007
P70

Application of a synthetic adsorbent resin (Diaion HP20) in fungal fermentation for natural products screening

Li-Ping Chang1, S. E. Urbance1, R. Bigelis2, J. A. Hucul1, B. Haltli1, and M. M. Wagenaar1. (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

Diaion HP20, a synthetic adsorbent resin, has been reported to improve production of secondary metabolites in many different microorganisms.  To increase the chance of finding novel bioactive secondary metabolites, the application of HP20 in fungal fermentation was investigated.  Fermentations with 97 fungi were carried out in the absence and presence of HP20 for 14 days, and extracts were generated.  The extracts were evaluated for their antimicrobial activities against Candida albicans and Staphylococcus aureus and for toxicity/BIA activities using Escherichia coli.  LCMS-ELSD was used to generate chemical profiles of the extracts.  When fermenting in the presence of HP20, an increase and decrease of antifungal activity was observed in 26% and 4% of the cultures, respectively; and similar results were also observed with antibacterial activity.  Percentages of cultures that produced cytotoxic metabolites in fermentation with and without HP20 addition were 9% and 4%, respectively.  Based on their chemical profiles, 62% of the cultures fermented with HP20 showed some increase in the peak area and/or the number of peaks, whereas only 13% of these cultures showed a decrease in production.  No difference in LCMS profile was observed with 25% of the cultures.  Addition of HP20 in fungal fermentations not only enhanced metabolite production but also increased the potential for finding novel fungal secondary metabolites.  Supplementing resin to fungal fermentation media is a useful and convenient approach to screen for novel fungal secondary metabolites and has been implemented in our natural products drug discovery programs.

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