World Applied Sciences Journal 20 (5): 742-747, 2012 ISSN 1818-4952 © IDOSI Publications, 2012 DOI: 10.5829/idosi.wasj.2012.20.05.2348 Corresponding Author: Fatemeh Ardestani, Department of Chemical Engineering, Islamic Azad University, Qaemshahr Branch, Qaemshahr, Iran, Tel: +98-1232145026, Fax: +98-1232240091, 742 L-isoleucine Effects on Yield and Productivity of a Batch Fermentation Process for Mycophenolic Acid Production by Penicillium brevicompactum Fatemeh Ardestani and Marzban Adel 1 2 Department of Chemical Engineering, Islamic Azad University, Qaemshahr Branch, Qaemshahr, Iran 1 Department of Chemical Engineering, Islamic Azad University, Tehran North Branch, Tehran, Iran 2 Abstract: Mycophenolic acid (MPA) is an antibiotic and immunosuppressive agent has been produced as a secondary metabolite of some fungi species such as Penicillium. In the present work, in the first step, mycophenolic acid production was performed in a fermentation process by Penicillium brevicompactum MUCL 19011 in shake flask using a base medium. Obtained results demonstrated the maximum MPA production, product yield and productivity of process as 1.38 g/L, 18.6 mg/g glucose and 4.9 mg/L. h, respectively. In the process time, the profiles of glucose utilization, biomass and MPA production were indicated and investigated. Using the base medium, mycophenolic acid was released at 180 hours after inoculation with an increasing profile and was reached to a maximum amount of 1.379 g/L at 280 h. Then, the profiles of MPA production, product yield and productivity of this fermentation process were evaluated using various concentrations of L-isoleucine in the culture medium. Results showed the maximum MPA production, product yield and process productivity were obtained by using of 4.5 g/L L-isoleucine as 1.84 g/L, 24.86 mg/g glucose and 6.57 mg/L. h, respectively. These values show an enhanced MPA production, product yield and process productivity as 33.4%, 33.6% and 34.1%, respectively. Key words: Batch fermentation %L-isoleucine %Penicillium brevicompactum %Mycophenolic acid INTRODUCTION inhibited replication of reo-virus strain T3D more than Mycophenolic acid is a relatively new antibiotic, anti- MPA also showed a good performance to overcome and fungal, anti-virus, anti-inflammation and control of human immunodeficiency virus (HIV), dengue immunosuppressive drug [1]. Mycophenolate mofetil (one virus infection as well as for lupus nephritis, reported in of MPA derivatives) is used widely in combination with some publications [7-11]. FDA approved MPA and some azathioprine and cyclosporine (CsA) as a triple therapy of its derivatives such as mycophenolate mofetil (MMF) method [2]. and sodium mycophenolate immunosuppressive drugs to Immunosuppressive agents are used in the initial decrease the incidence of graft rejection after organ days after transplantation in order to maintenance and transplantation [12]. reversal of established rejection. Mycophenolate mofetile The known mechanism of MPA action is an is used in the case of gastrointestinal symptoms (mainly inhibitory effect on a rate-limiting enzyme in novo diarrhea), neutropenia and mild anemia [3, 4]. biosynthetic pathway of purine nucleotides. This enzyme Base on some research reports, MPA has antiviral named inosine monophosphate dehydrogenase effects on some pathogenic viruses. One of these, are “IMPDH”. This inhibition process finally causes to stop Avian reo-viruses (ARV) cause viral arthritis and the biosynthesis of DNA and RNA and cell reproductivity tenosynovitis. MPA showed a good inhibitory effect on [13]. the replication of reo-viruses. Robertson et al. found that Different species of fungi has the ability to produce MPA concentrations of =3 µg/ml inhibited infectious ARV MPA as a secondary metabolite in their stationary phase progeny production by more than 100-fold [5]. Also, of growth. Based on the reported research results, at the Hermann et al. reported MPA in dosages of 30 µg/ml most cases, MPA is produced by Penicillium species 1000-fold and reo-virus strain T1L nearly 100-fold [6].