Enhancement of Lovastatin Production by Supplementing Polyketide Antibiotics to the Submerged Culture of Aspergillus terreus

Feedback inhibition existed in lovastatin biosynthesis from Aspergillus terreus. Exogenous lovastatin and other different polyketide antibiotics biosynthesized by polyketide synthase were supplemented to the cultures of A. terreus to investigate their influences on lovastatin production. Supplementing exogenous lovastatin of 100 mg l(-1) at the early stage of fermentation and the fast stage of its biosynthesis resulted in decreases of 76.4% and 20% in final lovastatin production, respectively. However, the fungal cell growth was not affected; the growing cycle was only prolonged in the submerged cultivation. Separate supplementation of the five kinds of polyketide antibiotics such as tylosin, erythromycin, tetracycline, daunorobin, and rifamycin to the cultures resulted in increases of about 20 similar to 25% in the final lovastatin production. Especially, supplementing tylosin of 50 mg l(-1) at the beginning of lovastatin biosynthesis led to the final lovastatin production of 952.7 +/- 24.3 mg l(-1), which was improved by 42% and 22% compared with that produced in the control and the original culture, respectively. These results are helpful to understand the regulations on lovastatin biosynthesis and improve the final desired metabolite contents in many antibiotics production.