Effects of lactose and glucose on production of itaconic acid and lovastatin by Aspergillus terreus ATCC 20542.

Fermentation products of Aspergillus terreus ATCC 20542 (a parent strain for lovastatin production) were collected, and the coexistence of itaconic acid (IA) with lovastatin was confirmed in this study. Using a lactose-based medium (LBM), lovastatin production was 873 mg/l on day 10, but IA production was only 22-28 mg/l during the cultures. When lactose in LBM was simply replaced with glucose, IA production was markedly enhanced by 20-fold (491 mg/l on day 5), which showed a growth-associated pattern. The findings indicated that the carbon source used (glucose or lactose) controlled the biosynthetic pathway. The net yield of lovastatin production when using lactose was calculated to be 25.1 mg/g (5.1-fold) in comparison with when using glucose in the cultures. Furthermore, lovastatin production was further increased by 9.2% when IA (0.5 g/l) was added to LBM. When IA was added at 5 g/l, the fermentation broth turned dark-brown, and lovastatin production was reduced by 18.0%. Hence, these two metabolites (IA and lovastatin) produced by the fungus might be related.

Application of oxygen vectors to Aspergillus terreus cultivation.

Research was undertaken to examine the effects of adding an oxygen carrier (n-dodecane, n-tetradecane, or n-hexadecane) on lovastatin production by Aspergillus terreus in both shaking-flask and 5-l fermentor cultivations. In the shaking-flask cultivation, an addition of 2.5% (w/v) n-dodecane to the medium gave about a 1.4-fold increase (0.51 g/l) in lovastatin production. This improvement was related to morphological changes in the fungal cells, and resulted mainly from the formation of small, uniform, compact pellets of A. terreus. In contrast, in the 5-l fermentor cultivation, the lovastatin production was only one-ninth of that achieved without n-dodecane addition independent of the pellet density. This adverse effect of adding the oxygen carrier to the medium was attributed to an uncontrolled, high dissolved oxygen level (higher than 60%) which resulted in unfavorable morphological changes and the formation of star-like pellets. However, when this dosage of n-dodecane was added 24 h after the start of the 5-l fermentor cultivation, lovastatin production was further enhanced due to its foam suppressing activity in the fungal fermentation.