Submerged Fermentation of Penicillium paxilli Biosynthesizing Paxilline, a Process Inhibited by Calcium-induced Sporulation

SUMMARY: A submerged fermentation process for the production of the tremorgenic mycotoxin paxilline by Penicillium paxilli has been developed. The fungus did not sporulate and accumulated paxilline to 1·5% (w/w) in freeze-dried cells within 6 d in a 60 1 stirred fermenter. Induction of extensive differentiation of conidiophores and profuse sporulation by adding 2% (w/v) CaCl2. 2H2O to the medium at batching reduced paxilline yield by 97%. Paxilline biosynthesis occurred when the glucose in the medium had been exhausted, implying that carbon catabolite repression may be involved in the biosynthesis of this alkaloid, even when calcium-induced sporulation inhibits or delays the onset of paxilline biosynthesis. Sporulation-induced inhibition of indole-terpenoid alkaloid biosynthesis in P. paxilli contrasts with the situation in some other penicillia elaborating indole alkaloids and allows disassociation of aspects of secondary metabolite biosynthesis from growth-associated differentiation, which formerly seemed to be linked.