Scale-up studies on a defined medium process for pilot plant production ofillicicolin by Gliocladium roseum

Illicicolin was cultivated at the 600-L pilot scale for purposes of materia l generation and process development. The initial medium containing oat flo ur was difficult operationally as a result of excessive foaming during ster ilization, so a new defined medium process (with either glucose or sucrose as the carbon source), developed at the 23-L scale, was scaled up and impro ved for pilot scale needs. Pilot scale media development efforts focused on exploring the highest concentration of media (1.0 x to 3.0x) that could be cultivated at the pilot scale and not be limited by mixing or oxygen mass transfer. The process was scaled up successfully and peak titers improved 7 .5-fold, from about 200 mg/L in the initial complex medium to 1500 mg/L in the final defined medium.