History of yield improvements in the production of asperlicin byAspergillus alliaceus

The natural product asperlicin is the first nonpeptide antagonist of cholecystokinin isolated from a microbial source. At discovery, production of asperlicin by the original soil isolate ofAspergillus alliaceus was between 15 and 30 mg/l. Selection of natural variants ofA. alliaceus, use of Plackett & Burman and Simplex experimental designs; formulation of synthetic media; amino acid supplementation of production media; analysis of complex nitrogen sources for their amino acid content; evaluation of promising media in fermentors; substitution of glycerol for glucose as a carbon source and rational mutant selection all contributed to titer increases to >900 mg/l.