Enhanced Mycophenolic Acid Production by Penicillium brevicompactum with Enzymatically Hydrolyzed Casein
Mycophenolic acid (MPA) is a secondary metabolite
produced by Penicillium brevicompactum, which has antibiotic and
immunosuppressive properties. In this study, the first, mycophenolic
acid was produced in a fermentation process by Penicillium
brevicompactum MUCL 19011 in shake flask using a base medium.
The maximum MPA production, product yield and productivity of
process were 1.379 g/L, 18.6 mg/g glucose and 4.9 mg/L. h,
respectively. Also the glucose consumption, biomass and MPA
production profiles were investigated during batch cultivation.
Obtained results showed that MPA production starts approximately
after 180 hours and reaches to a maximum at 280 h. In the next step,
the effects of some various concentrations of enzymatically
hydrolyzed casein on MPA production were evaluated. Maximum
MPA production, product yield and productivity as 3.63 g/L, 49
mg/g glucose and 12.96 mg/L.h, respectively were obtained with
using 30 g/L enzymatically hydrolyzed casein in culture medium.
These values show an enhanced MPA production, product yield and
process productivity pr as 116.8%, 132.8% and 163.2%, respectively.
[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] Bartman, C. D.; Doerfler, D. L.; Bird, B. A.; Remaley, A. T.; Peace, J.
N.; Campbell, I. M. mycophenolic acid production by Penicillium
brevicompactum on solid media, App. Environ. Microb, 1981, Pp 729-
736. .
[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] 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.
[12] Alania, F.; Grove, J. A.; Anderson, W. A.; Young , M. M.
Mycophenolic acid production in solid-state fermentation using a
packed-bed bioreactor, Biochem. Eng, 2009, 44, 106-110.
[13] Bahrami, G.; Mohammadi, B. An isocratic high performance liquid
chromatographic method for quantification of mycophenolic acid and
its glucuronide metabolite in human serum using liquid liquid
extraction: Application to human pharmacokinetic studies, Clinica
Chimica Acta, 2006, 370, Pp 185-190.
[14] 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
[15] www.brenda.com
[16] Masurekar, P. S., Demain, A. Insensitivity of homocitrate synthase in
extracts of Penicillium chyrosogenum to feedback inhibition by lysine,
Appl. Microbiol, 1974, 28 (2), Pp 265-270
[17] C. T. Bedford, C. Fairlipe, Sequence Studies in Biosynthesis;
Mycophenolic Acid, Chem. Com. 1971, pp. 323-324.
[18] 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.
[19] 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.
[20] F. Ardestani, S.A. Fatemi, B. Yakhchali, M. Hosseyni, G. Najafpour,
The effects of methionine and acetate concentrations on mycophenolic
acid production by Penicillium bervicompactum MUCL 19011 in
submerged culture, Int. J. of Natural Sciences and Engineering, 2009
(2:2), pp. 83-86.
[21] Karaffa, L.; Sandor, E.; Kozma, J.; Szentirmai, A. Methionine enhances
sugar consumption, fragmentation, vacuolation and cephalosporin-C
production in Acremonium chrysogenum, Process Biochem, 1997, 32
(6), 495-499.
[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] Bartman, C. D.; Doerfler, D. L.; Bird, B. A.; Remaley, A. T.; Peace, J.
N.; Campbell, I. M. mycophenolic acid production by Penicillium
brevicompactum on solid media, App. Environ. Microb, 1981, Pp 729-
736. .
[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] 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.
[12] Alania, F.; Grove, J. A.; Anderson, W. A.; Young , M. M.
Mycophenolic acid production in solid-state fermentation using a
packed-bed bioreactor, Biochem. Eng, 2009, 44, 106-110.
[13] Bahrami, G.; Mohammadi, B. An isocratic high performance liquid
chromatographic method for quantification of mycophenolic acid and
its glucuronide metabolite in human serum using liquid liquid
extraction: Application to human pharmacokinetic studies, Clinica
Chimica Acta, 2006, 370, Pp 185-190.
[14] 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
[15] www.brenda.com
[16] Masurekar, P. S., Demain, A. Insensitivity of homocitrate synthase in
extracts of Penicillium chyrosogenum to feedback inhibition by lysine,
Appl. Microbiol, 1974, 28 (2), Pp 265-270
[17] C. T. Bedford, C. Fairlipe, Sequence Studies in Biosynthesis;
Mycophenolic Acid, Chem. Com. 1971, pp. 323-324.
[18] 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.
[19] 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.
[20] F. Ardestani, S.A. Fatemi, B. Yakhchali, M. Hosseyni, G. Najafpour,
The effects of methionine and acetate concentrations on mycophenolic
acid production by Penicillium bervicompactum MUCL 19011 in
submerged culture, Int. J. of Natural Sciences and Engineering, 2009
(2:2), pp. 83-86.
[21] Karaffa, L.; Sandor, E.; Kozma, J.; Szentirmai, A. Methionine enhances
sugar consumption, fragmentation, vacuolation and cephalosporin-C
production in Acremonium chrysogenum, Process Biochem, 1997, 32
(6), 495-499.
@article{"International Journal of Chemical, Materials and Biomolecular Sciences:64651", author = "F. Ardestani and S. S. A. Fatemi and B. Yakhchali", title = "Enhanced Mycophenolic Acid Production by Penicillium brevicompactum with Enzymatically Hydrolyzed Casein", abstract = "Mycophenolic acid (MPA) is a secondary metabolite
produced by Penicillium brevicompactum, which has antibiotic and
immunosuppressive properties. In this study, the first, mycophenolic
acid was produced in a fermentation process by Penicillium
brevicompactum MUCL 19011 in shake flask using a base medium.
The maximum MPA production, product yield and productivity of
process were 1.379 g/L, 18.6 mg/g glucose and 4.9 mg/L. h,
respectively. Also the glucose consumption, biomass and MPA
production profiles were investigated during batch cultivation.
Obtained results showed that MPA production starts approximately
after 180 hours and reaches to a maximum at 280 h. In the next step,
the effects of some various concentrations of enzymatically
hydrolyzed casein on MPA production were evaluated. Maximum
MPA production, product yield and productivity as 3.63 g/L, 49
mg/g glucose and 12.96 mg/L.h, respectively were obtained with
using 30 g/L enzymatically hydrolyzed casein in culture medium.
These values show an enhanced MPA production, product yield and
process productivity pr as 116.8%, 132.8% and 163.2%, respectively.", keywords = "Penicillium brevicompactum, Enzymatically
hydrolyzed casein, Mycophenolic acid, Submerged culture", volume = "5", number = "1", pages = "94-4", }
