Monday, July 30, 2007
P4

Significant enhancement in the production of primary(itaconic acid) and secondary metabolites(lovastatin) through surfactant addition in fermentations of high-yielding permeabilized mutants of Aspergillus terreus

W.S. Shin1, Y.M. Jang1, Y.S. Jeong2, J.D. Lee3, P.H. Kim1, S.W. Yie1, D.W. Seo1, and G.T. Chun1. (1) School of Bioscience and Biotechnology, Kangwon National University, Hyoja 2-dong, Chunchon 200-701, South Korea, (2) Faculty of Biotechnology, Chonbuk National University, Deokjin-dong, Jeonju 561-756, South Korea, (3) Korea Institute of Industrial Technology, Ipchang-Myun, Cheonan 330-825, South Korea

Filamentous fungal cells of Aspergillus terreus are welll known as a industrial microorganism responsible for the production of both itaconic acid (primary metabolite) and lovastatin (secondary metabolite). Itaconic acid produced by the fungus as a primary metabolite belongs to a carboxylic acid used in the manufacture of synthetic resins, whereas lovastatin biosynthesized as a secondary metabolite by the same microorganism under the specific culture conditions is a powerful anti-cholesterolemic agent. During the intensive courses of strain development, it was observed that production levels of itaconic acid as well as lovastatin were remarkably increased when optimum amount of surfactants such as triton X-100 and/or tween-80 was supplemented in the respective fermentation medium (approximately 3 and 5 times higher productivity in the case of itaconic acid and lovastatin, respectively). It was assumed that these phenomena should be related to the special roles of membrane permeability of the high-yielding mutants with the properties of resistance against high concentrations of nystatin, a polyene antifungal antibiotic. In parallel with the strain development, medium optimization process was carried out in order to find optimal composition of the respective production medium (including the surfactants) for each metabolite, using powerful statistical methods such as fractional factorial design(FFD), steepest ascent method and response surface method (RSM). It was concluded that not only the optimized production medium but also good morphology of the high-yielding producers was responsible for the significant increase in the production of both itaconic acid and lovastatin.