The Effects of Methionine and Acetate Concentrations on Mycophenolic Acid Production by Penicillium bervicompactum MUCL 19011 in Submerged Culture
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.
[1] T.Rainiene, Immunosuppression in the past and today, Acta Medica
Lituanica. 2005, pp. 10-17.
[2] S. Tian, P. Mele, F. Halloran, The use of mycophenolate mofetil in
transplant recipients, J. Immunopharma. 2000, pp. 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. 2003, pp. 31-37.
[4] C. D. Bartman, et al, Mycophenolic Acid Production by Penicillium
brevicompactum on Solid Media, Appl. Environ. Microbiol. 1981, pp.
729-736.
[5] D. L. Doerfler, C. D. Bartman, L. M. Campbell, Mycophenolic acid
production by Penicillium brevicompactum in two media. Can. J.
Microbiol. 1979, pp. 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., 2005, Pp 83-86.
[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. 2005, pp. 83-86.
[8] A. Sircar, et al. Manufacture and purification of mycophenolic acid,
United States Patent. PCT No.: PCT/INOO/00017 , 2003.
[9] O. Puel, S. Tadrist, et al, Byssochlamys nivea as a source of
mycophenolic acid, Appl. Environ. Microbiol. 2005, pp. 550-553.
[10] P. Lafont, J. Debeaupuis, M. Gaillardia, J. Payen, Production of
mycophenolic acid by Penicillium roqueforti strains, Appl. Environ.
Microbiol. 1978, pp. 365-368.
[11] J. L. Adrio, A. L. Demain, Fungal biotechnology, Int. Microbiol, 2003,
pp. 191-199.
[12] Z. Xu, S. Yang, Production of mycophenolic acid by Penicillium
brevicompactum immobilized in a rotating fibrous-bed bioreactor,
Enzyme Microb. Technol. 2007, pp. 623-628.
[13] C. T. Bedford, C. Fairlipe, Sequence Studies in Biosynthesis;
Mycophenolic Acid, Chem. Com. 1971, pp. 323-324.
[14] W. L. Muth, I. Nash, Biosynthesis of mycophenolic acid: purification
and characterization of S-adenosyl-L-methionine:
demethylmycophenolic acid o-methyltransferase, Antimicrob. Chemo.
1975, pp. 321-327.
[15] A. Fawzy, A. Elbarbry, Simple high performance liquid
chromatographic assay for mycophenolic acid in renal transplant
patients, J. Pharma. Biomedica. Ana. 2007, pp. 788-792
[16] 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.
1987, pp. 2509-2514.
[17] 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, 1999, pp. 33-38).
[1] T.Rainiene, Immunosuppression in the past and today, Acta Medica
Lituanica. 2005, pp. 10-17.
[2] S. Tian, P. Mele, F. Halloran, The use of mycophenolate mofetil in
transplant recipients, J. Immunopharma. 2000, pp. 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. 2003, pp. 31-37.
[4] C. D. Bartman, et al, Mycophenolic Acid Production by Penicillium
brevicompactum on Solid Media, Appl. Environ. Microbiol. 1981, pp.
729-736.
[5] D. L. Doerfler, C. D. Bartman, L. M. Campbell, Mycophenolic acid
production by Penicillium brevicompactum in two media. Can. J.
Microbiol. 1979, pp. 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., 2005, Pp 83-86.
[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. 2005, pp. 83-86.
[8] A. Sircar, et al. Manufacture and purification of mycophenolic acid,
United States Patent. PCT No.: PCT/INOO/00017 , 2003.
[9] O. Puel, S. Tadrist, et al, Byssochlamys nivea as a source of
mycophenolic acid, Appl. Environ. Microbiol. 2005, pp. 550-553.
[10] P. Lafont, J. Debeaupuis, M. Gaillardia, J. Payen, Production of
mycophenolic acid by Penicillium roqueforti strains, Appl. Environ.
Microbiol. 1978, pp. 365-368.
[11] J. L. Adrio, A. L. Demain, Fungal biotechnology, Int. Microbiol, 2003,
pp. 191-199.
[12] Z. Xu, S. Yang, Production of mycophenolic acid by Penicillium
brevicompactum immobilized in a rotating fibrous-bed bioreactor,
Enzyme Microb. Technol. 2007, pp. 623-628.
[13] C. T. Bedford, C. Fairlipe, Sequence Studies in Biosynthesis;
Mycophenolic Acid, Chem. Com. 1971, pp. 323-324.
[14] W. L. Muth, I. Nash, Biosynthesis of mycophenolic acid: purification
and characterization of S-adenosyl-L-methionine:
demethylmycophenolic acid o-methyltransferase, Antimicrob. Chemo.
1975, pp. 321-327.
[15] A. Fawzy, A. Elbarbry, Simple high performance liquid
chromatographic assay for mycophenolic acid in renal transplant
patients, J. Pharma. Biomedica. Ana. 2007, pp. 788-792
[16] 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.
1987, pp. 2509-2514.
[17] 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, 1999, pp. 33-38).
@article{"International Journal of Chemical, Materials and Biomolecular Sciences:52463", author = "F. Ardestani and S.A. Fatemi and B. Yakhchali and M. Hosseyni and G. Najafpour", title = "The Effects of Methionine and Acetate Concentrations on Mycophenolic Acid Production by Penicillium bervicompactum MUCL 19011 in Submerged Culture", 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", volume = "3", number = "3", pages = "137-4", }