The Effect of Methionine and Acetate Concentrations on Mycophenolic Acid Production by Penicillium bervicompactum MUCL 19011 in Submerged Culture

Authors: Fatemeh Ardestani, Seyed Safa-ali Fatemi, Bagher Yakhchali, Seyed Morteza Hosseyni, Ghasem Najafpour

Abstract:

Mycophenolic acid “MPA" is a secondary metabolite of Penicillium bervicompactum with antibiotic and immunosuppressive properties. In this study, fermentation process was established for production of mycophenolic acid by Penicillium bervicompactum MUCL 19011 in shake flask. The maximum MPA production, product yield and productivity were 1.379 g/L, 18.6 mg/g glucose and 4.9 mg/L.h respectively. Glucose consumption, biomass and MPA production profiles were investigated during fermentation time. It was found that MPA production starts approximately after 180 hours and reaches to a maximum at 280 h. In the next step, the effects of methionine and acetate concentrations on MPA production were evaluated. Maximum MPA production, product yield and productivity (1.763 g/L, 23.8 mg/g glucose and 6.30 mg/L. h respectively) were obtained with using 2.5 g/L methionine in culture medium. Further addition of methionine had not more positive effect on MPA production. Finally, results showed that the addition of acetate to the culture medium had not any observable effect on MPA production

Keywords: Penicillium bervicompactum, Methionine, Mycophenolic acid, Submerged culture.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1060004

References:

[1] T.Rainiene, Immunosuppression in the past and today, Acta Medica Lituanica. 12 No. 3 (2005)10-17.
[2] S. Tian, P. Mele, F. Halloran, The use of mycophenolate mofetil in transplant recipients, J. Immunopharma. 47 (2000) 215-245.
[3] A.Charlotte, J. Hans Charleston, Mycophenolic acid inhibits inosine 5- monophosphate dehydrogenase and suppresses immunoglobulin and cytokine production of B cells, Int. Immunopharma. 3 (2003) 31-37.
[4] C. D. Bartman, et al, Mycophenolic Acid Production by Penicillium brevicompactum on Solid Media, Appl. Environ. Microbiol. (1981) 729-736.
[5] D. L. Doerfler, C. D. Bartman, L. M. Campbell, Mycophenolic acid production by Penicillium brevicompactum in two media. Can. J. Microbiol. 25 (1979) 940-943.
[6] Vinokurova, NG., Ivanushkina, NE., Kochkina, GA., Arinbasarov, MU., Ozer-skaya, SM., Production of mycophenolic acid by fungi of the genus Penicillium link, Appl Biochem Microbiol., 41, Pp 83-6 (2005).
[7] N. Vinokurova, N. Ivanushkina, G. Kochkina, M. Arinbasarov, S. Ozerskaya, Production of mycophenolic acid by fungi of the genus Penicillium link, Appl. Biochem. Microbiol. 41 (2005) 83-86.
[8] J. L. Adrio, A. L. Demain, Fungal biotechnology, Int. Microbiol. 6 (2003) 191-199.
[9] Z. Xu, S. Yang, Production of mycophenolic acid by Penicillium brevicompactum immobilized in a rotating fibrous-bed bioreactor, Enzyme Microb. Technol. 40 (2007) 623-628.
[10] A. Sircar, et al. Manufacture and purification of mycophenolic acid, United States Patent. PCT No.: PCT/INOO/00017 (2003).
[11] C. T. Bedford, C. Fairlipe, Sequence Studies in Biosynthesis; Mycophenolic Acid, Chem. Com. (1971) 323-324.
[12] A. Fawzy, A. Elbarbry, Simple high performance liquid chromatographic assay for mycophenolic acid in renal transplant patients, J. Pharma. Biomedica. Ana. 43 (2007) 788-792
[13] W. L. Muth, I. Nash, Biosynthesis of mycophenolic acid: purification and characterization of S-adenosyl-L-methionine: demethylmycophenolic acid o-methyltransferase, Antimicrob. Chemo. 8 No 3 (1975) 321-327.
[14] S. AK, M. MR, K. RA, M. EVS, et al., Optimization of mycophenolic acid production in solid state fermentation using response surface methodology. J Ind Microbiol Biotechnol, 22, Pp 33-38 (1999). M.
[15] H. Ozaki, M. Ishihara, T. Kida, S. Yamanaka, H. Shibai, Mycophenolic acid production by drug-resistant and methionine or glutamic-acid requiring mutants of Penicillium brevicopactum, Agric Biol Chem. 51 (1987) 2509-2514.
[16] O. Puel, S. Tadrist, et al, Byssochlamys nivea as a source of mycophenolic acid, Appl. Environ. Microbiol. 71 No 1 (2005) 550-553.
[17] P. Lafont, J. Debeaupuis, M. Gaillardia, J. Payen, Production of mycophenolic acid by Penicillium roqueforti strains, Appl. Environ. Microbiol. 37 (1978) 365-368.