Effects of medium sterilization on the production of zaragozic acids by the fungusLeptodontidium elatius

The production of zaragozic acids by fermentation of the fungusLeptodontidium elatius was examined at the 800-L fermentor scale under two different production medium batch sterilization conditions. Low production-medium heat input (R0=33.4 min) resulted in a 4′-desacetoxy zaragozic acid C:4′-O-desacetyl zaragozic acid C:zaragozic acid C ratio of 0.53:0.60:1.0. At a higher heat input (R0=50.5 min), the ratio shifted to 1.0:0.66:1.0 with a corresponding 26% increase in total zaragozic acid production. This higher total zaragozic acid titer resulted from an increase in the amount of 4′-desacetoxy zaragozic acid C produced while the levels of the other two analogues remained unchanged. Batch sterilization conditions also resulted in differences in growth, carbon substrate consumption, and oxygen uptake rates. The structures of the zaragozic acids produced suggest a precursor/end product relationship. A biosynthetic model describing the synthesis of the three zaragozic acids listed above is postulated and used to explain the effects of production-medium heat input during sterilization.