scholarly journals Production of mycophenolic acid by Penicillium brevicompactum—A comparison of two methods of optimization

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

Mycophenolic acid is produced during balanced growth of Penicillium brevicompactum

1977 ◽  
Vol 23 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Carter P. Nulton ◽  
Iain M. Campbell
Keyword(s):  
Dilution Rate ◽  
Secondary Metabolite ◽  
Mycophenolic Acid ◽  
Continuous Flow ◽  
Acid Production ◽  
Flow System ◽  
Metabolic System ◽  
Balanced Growth ◽  
Secondary Metabolite Biosynthesis ◽  
Penicillium Brevicompactum

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.

scholarly journals Construction of a Codon-Adapted Nourseotricin-Resistance Marker Gene for Efficient Targeted Gene Deletion in the Mycophenolic Acid Producer Penicillium brevicompactum

2019 ◽  
Vol 5 (4) ◽  
pp. 96
Author(s):  
Yasaman Mahmoudjanlou ◽  
Birgit Hoff ◽  
Ulrich Kück
Keyword(s):  
Mycophenolic Acid ◽  
Marker Gene ◽  
Wild Type ◽  
Resistance Marker ◽  
Subsequent Transformation ◽  
Targeted Gene Deletion ◽  
Filamentous Ascomycete ◽  
Wild Type Phenotype ◽  
Penicillium Brevicompactum ◽  
Resistance Markers

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.

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
Keyword(s):  
Mycophenolic Acid ◽  
Acid Production ◽  
Submerged Cultures ◽  
Penicillium Brevicompactum

Mycotoxin Production and Postharvest Storage Rot of Ginger (Zingiber officinale) by Penicillium brevicompactum

2005 ◽  
Vol 68 (3) ◽  
pp. 607-609 ◽  
Author(s):  
D. P. OVERY ◽  
J. C. FRISVAD
Keyword(s):  
Secondary Metabolites ◽  
Mycophenolic Acid ◽  
Zingiber Officinale ◽  
Human Consumption ◽  
Mold Growth ◽  
Plant Food ◽  
Predominant Species ◽  
Tissue Extracts ◽  
Penicillium Brevicompactum ◽  
Fungal Secondary Metabolites

Twenty naturally infected ginger (Zingiber officinale) rhizomes displaying visible mold growth were examined to identify the fungi and to evaluate the presence of fungal secondary metabolites. Penicillium brevicompactum was the predominant species isolated from 85% of the samples. Mycophenolic acid was identified from corresponding tissue extracts. Because mycophenolic acid is a potent immunosuppressant and synergistic mycotoxicosis studies involving human consumption have not been carried out on this metabolite, spoilage of commercially marketed produce caused by P. brevicompactum is a concern. This is the first reported occurrence of mycophenolic acid in commercially sold plant food products.

scholarly journals Mycophenolic Acid Production by Penicillium brevicompactum on Solid Media

1981 ◽  
Vol 41 (3) ◽  
pp. 729-736 ◽  
Author(s):  
C. D. Bartman ◽  
D. L. Doerfler ◽  
B. A. Bird ◽  
A. T. Remaley ◽  
J. N. Peace ◽  
...  
Keyword(s):  
Mycophenolic Acid ◽  
Acid Production ◽  
Solid Media ◽  
Penicillium Brevicompactum

Mycophenolic acid production by Penicillium brevicompactum in two media

1979 ◽  
Vol 25 (8) ◽  
pp. 940-943 ◽  
Author(s):  
D. L. Doerfler ◽  
C. D. Bartman ◽  
I. M. Campbell
Keyword(s):  
Secondary Metabolism ◽  
Mycophenolic Acid ◽  
Acid Production ◽  
Solid Culture ◽  
Simple Medium ◽  
Penicillium Brevicompactum ◽  
Fungal Secondary Metabolism

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.

scholarly journals Involvement of a Natural Fusion of a Cytochrome P450 and a Hydrolase in Mycophenolic Acid Biosynthesis

2012 ◽  
Vol 78 (14) ◽  
pp. 4908-4913 ◽  
Author(s):  
Bjarne Gram Hansen ◽  
Ewelina Mnich ◽  
Kristian Fog Nielsen ◽  
Jakob Blæsbjerg Nielsen ◽  
Morten Thrane Nielsen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Gene Cluster ◽  
Mycophenolic Acid ◽  
Polyketide Synthase ◽  
Fusion Gene ◽  
Bioinformatic Analysis ◽  
Terminal Region ◽  
Ring Closure ◽  
Content Type ◽  
Penicillium Brevicompactum

ABSTRACTMycophenolic acid (MPA) is a fungal secondary metabolite and the active component in several immunosuppressive pharmaceuticals. The gene cluster coding for the MPA biosynthetic pathway has recently been discovered inPenicillium brevicompactum, demonstrating that the first step is catalyzed by MpaC, a polyketide synthase producing 5-methylorsellinic acid (5-MOA). However, the biochemical role of the enzymes encoded by the remaining genes in the MPA gene cluster is still unknown. Based on bioinformatic analysis of the MPA gene cluster, we hypothesized that the step following 5-MOA production in the pathway is carried out by a natural fusion enzyme MpaDE, consisting of a cytochrome P450 (MpaD) in the N-terminal region and a hydrolase (MpaE) in the C-terminal region. We verified that the fusion gene is indeed expressed inP. brevicompactumby obtaining full-length sequence of thempaDEcDNA prepared from the extracted RNA. Heterologous coexpression ofmpaCand the fusion genempaDEin the MPA-nonproducerAspergillus nidulansresulted in the production of 5,7-dihydroxy-4-methylphthalide (DHMP), the second intermediate in MPA biosynthesis. Analysis of the strain coexpressingmpaCand thempaDpart ofmpaDEshows that the P450 catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). DHMB is then converted to DHMP, and our results suggest that the hydrolase domain aids this second step by acting as a lactone synthase that catalyzes the ring closure. Overall, the chimeric enzyme MpaDE provides insight into the genetic organization of the MPA biosynthesis pathway.

MYCOPHENOLIC ACID AN ANTIBIOTIC FROM PENICILLIUM BREVICOMPACTUM DIERCKX

The Lancet ◽  
1946 ◽  
Vol 247 (6385) ◽  
pp. 46-49 ◽  
Author(s):  
H.W. Florey ◽  
M.A. Jennings ◽  
K. Gilliver ◽  
A.G. Sanders
Keyword(s):  
Mycophenolic Acid ◽  
Penicillium Brevicompactum
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