Evaluation of mycophenolic acid production by Penicillium brevicompactum MUCL 19011 in batch and continuous submerged cultures

2010 ◽  
Vol 50 (3) ◽  
pp. 99-103 ◽  
Author(s):  
Fatemeh Ardestani ◽  
Seyed Safa-ali Fatemi ◽  
Bagher Yakhchali ◽  
Seyed Morteza Hosseyni ◽  
Ghasem Najafpour
1977 ◽  
Vol 23 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Carter P. Nulton ◽  
Iain M. Campbell

When Penicillium brevicompactum is grown on Czapek Dox medium in the surface or sub merged mode as batch or continuous-flow cultures, mycophenolic acid is produced. Unlike the classical secondary metabolic system, 6-methylsalicylic acid production by P. patulum, mycophenolic acid is formed independently of dilution rate in a flow system. Discounting the possibility that strains of P. brevicompactum that produce mycophenolic acid are mutants defective in the control of secondary metabolite biosynthesis, we conclude that mycophenolic acid production is not regulated as part of a non-vegetative genome. An invertase (EC 3.2.1.26) activity has been encountered in both P. brevicompactum and P. patulum.


1981 ◽  
Vol 41 (3) ◽  
pp. 729-736 ◽  
Author(s):  
C. D. Bartman ◽  
D. L. Doerfler ◽  
B. A. Bird ◽  
A. T. Remaley ◽  
J. N. Peace ◽  
...  

1979 ◽  
Vol 25 (8) ◽  
pp. 940-943 ◽  
Author(s):  
D. L. Doerfler ◽  
C. D. Bartman ◽  
I. M. Campbell

Penicillium brevicompactum produces mycophenolic acid as it grows vegetatively, not only on a simple medium where growth is slow but also on a richer medium where growth is less restricted. The implications of this finding on the association of fungal secondary metabolism with the idiophase in liquid and solid culture are discussed.


1987 ◽  
Vol 51 (9) ◽  
pp. 2509-2514 ◽  
Author(s):  
Hachiro OZAKI ◽  
Masaru ISHIHARA ◽  
Takao KIDA ◽  
Shigeru YAMANAKA ◽  
Hiroshiro SHIBAI

2014 ◽  
Vol 7 (3) ◽  
pp. 321-328 ◽  
Author(s):  
V. Séguin ◽  
S. Gente ◽  
N. Heutte ◽  
P. Vérité ◽  
V. Kientz-Bouchart ◽  
...  

Mycophenolic acid is considered as an immunosuppressive pharmaceutical drug, but also as a mycotoxin due to its undesirable presence in various feedstuffs. Although Penicillium brevicompactum has been historically identified as the major producer of mycophenolic acid, this study reports for the first time the production of mycophenolic acid by isolates of Eurotium repens collected from agricultural and indoor environments. Fungal identification was achieved by scanning electron microscopy and molecular techniques, and mycophenolic acid production was confirmed by two analytical methods (gas and liquid chromatography coupled to mass spectrometry). These findings suggest that mycophenolic acid production and immunosuppressive properties of other closely related Eurotium should be evaluated in future studies.


2021 ◽  
Vol 12 (1) ◽  
pp. 366-376

Mycophenolic acid (MPA) is, due to its immunosuppressive and biological activities, a potential compound. It is the secondary metabolite produced in submerged cultivation by the microfungus Penicillium brevicompactum. Batch, fed-batch, and continuous mode of cultivation for mycophenolic acid production were performed and compared in the current work. To increase productivity, mycophenolic acid production was studied in batch, fed-batch, and continuous bioreactors. These experiments were conducted with a 2.5 L working volume in a 3.7 L continuous stirred tank bioreactor. In all cases, operating conditions such as temperature, pH, agitation, and aeration, 28 °C, 5.5, 200 rpm, and 2 vvm, respectively, were the same. In fed-batch fermentation, the MPA concentration obtained was 1.91 g/L higher than the value obtained in batch culture, 1.55 g/L, while in continuous fermentation, 1.67 g/L was obtained. The mycophenolic acid productivity obtained in the continuous fermentation process was 0.025 g/L/h, which was maximum MPA productivity, compared to 0.007 g/L/h in the fed-batch fermentation process and 0.006 g/L/h in the batch fermentation process. The impact of substrate inhibition on the product formation can effectively bring down by continuous fermentation processes. The MPA productivity was increased in continuous fermentation relative to batch and fed-batch processing. The finding indicates that continuous culture of Penicillium brevicompactum is a promising strategy for the synthesis of mycophenolic acid.


2019 ◽  
Vol 5 (4) ◽  
pp. 96
Author(s):  
Yasaman Mahmoudjanlou ◽  
Birgit Hoff ◽  
Ulrich Kück

Penicillium brevicompactum is a filamentous ascomycete used in the pharmaceutical industry to produce mycophenolic acid, an immunosuppressant agent. To extend options for genetic engineering of this fungus, we have tested two resistance markers that have not previously been applied to P. brevicompactum. Although a generally available phleomycin resistance marker (ble) was successfully used in DNA-mediated transformation experiments, we were not able to use a commonly applicable nourseothricin resistance cassette (nat1). To circumvent this failure, we constructed a new nat gene, considering the codon bias for P. brevicompactum. We then used this modified nat gene in subsequent transformation experiments for the targeted disruption of two nuclear genes, MAT1-2-1 and flbA. For MAT1-2-1, we obtained deletion strains with a frequency of about 10%. In the case of flbA, the frequency was about 4%, and this disruption strain also showed reduced conidiospore formation. To confirm the deletion, we used ble to reintroduce the wild-type genes. This step restored the wild-type phenotype in the flbA deletion strain, which had a sporulation defect. The successful transformation system described here substantially extends options for genetically manipulating the biotechnologically relevant fungus P. brevicompactum.


2016 ◽  
Vol 11 ◽  
pp. 77-85 ◽  
Author(s):  
Gopal Patel ◽  
Mahesh D. Patil ◽  
Surbhi Soni ◽  
Taresh P. Khobragade ◽  
Yusuf Chisti ◽  
...  

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