Monday, July 27, 2009
P2
Fermentative production of self-toxic fungal secondary metabolites
Fungi are well known for their vast diversity of secondary metabolites that include many life-saving drugs and highly toxic mycotoxins. In general, fungal cultures producing such metabolites are immune to their toxic effects, but some are known to produce self-toxic compounds and pose production optimization challenges if such metabolites are needed in large amounts for chemical modification or clinical testing. One such culture was identified as the lead for one of our exploratory projects. This culture was found to be a slow grower, produced trace amounts of the target metabolite under the standard fermentation conditions, and extensive medium optimization studies failed to yield higher titers. The target compound was later found to be toxic to the producer with MIC of 8-16 mg/L. Fermentations carried out in medium containing HP20 resin (1 to 5% w/v) afforded significantly higher titers, but 3% wet resin (w/v) was found to be optimum for the production train. Use of a neutral adsorbent resin in the medium increased the titer of the target compound from ~5 mg/L to ~400 mg/L range. Several examples of resin-based fermentations of soil streptomyces are in the published literature, but this may be the first for a fungal fermentation requiring the addition of resin to improve metabolite production. Further details of the studies and factors affecting the day-to-day variation in the titer will be discussed.
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See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)
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See more of The Annual Meeting and Exhibition 2009 (July 26 - 30, 2009)