Search Results (4)

Beta (β)-lactam antibiotic is an industrially important molecule produced by Penicillium chrysogenum/rubens. Penicillin is a building block for 6-aminopenicillanic acid (6-APA), an important active pharmaceutical intermediate (API) used for semi-synthetic antibiotics biosynthesis. In this investigation, we isolated and identified Penicillium chrysogenum, P. rubens, P. brocae, P. citrinum, Aspergillus fumigatus, A. sydowii, Talaromyces tratensis, Scopulariopsis brevicaulis, P. oxalicum, and P. dipodomyicola using the internal transcribed spacer (ITS) region and the β-tubulin (BenA) gene for precise species identification from Indian origin. Furthermore, the BenA gene distinguished between complex species of P. chrysogenum and P. rubens to a certain extent which partially failed by the ITS region. In addition, these species were distinguished by metabolic markers profiled by liquid chromatography–high resolution mass spectrometry (LC-HRMS). Secalonic acid, Meleagrin, and Roquefortine C were absent in P. rubens. The crude extract evaluated for PenV production by antibacterial activities by well diffusion method against Staphylococcus aureus NCIM-2079. A high-performance liquid chromatography (HPLC) method was developed for simultaneous detection of 6-APA, phenoxymethyl penicillin (PenV), and phenoxyacetic acid (POA). The pivotal objective was the development of an indigenous strain portfolio for PenV production. Here, a library of 80 strains of P. chrysogenum/rubens was screened for PenV production. Results showed 28 strains capable of producing PenV in a range from 10 to 120 mg/L when 80 strains were screened for its production. In addition, fermentation parameters, precursor concentration, incubation period, inoculum size, pH, and temperature were monitored for the improved PenV production using promising P. rubens strain BIONCL P45. In conclusion, P. chrysogenum/rubens strains can be explored for the industrial-scale PenV production. Full article

The discovery of penicillin entailed a decisive breakthrough in medicine. No other medical advance has ever had the same impact in the clinical practise. The fungus Penicillium chrysogenum (reclassified as P. rubens) has been used for industrial production of penicillin ever since the forties of the past century; industrial biotechnology developed hand in hand with it, and currently P. chrysogenum is a thoroughly studied model for secondary metabolite production and regulation. In addition to its role as penicillin producer, recent synthetic biology advances have put P. chrysogenum on the path to become a cell factory for the production of metabolites with biotechnological interest. In this review, we tell the history of P. chrysogenum, from the discovery of penicillin and the first isolation of strains with high production capacity to the most recent research advances with the fungus. We will describe how classical strain improvement programs achieved the goal of increasing production and how the development of different molecular tools allowed further improvements. The discovery of the penicillin gene cluster, the origin of the penicillin genes, the regulation of penicillin production, and a compilation of other P. chrysogenum secondary metabolites will also be covered and updated in this work. Full article

The filamentous fungus Penicillium chrysogenum (recently reidentified as Penicillium rubens) is used in the industrial production of the β-lactam antibiotic penicillin. There are several mechanisms regulating the production of this antibiotic, acting both at the genetic and epigenetic levels, the latter including the modification of chromatin by methyltransferases. S-adenosyl-L-methionine (AdoMet) is the main donor of methyl groups for methyltransferases. In addition, it also acts as a donor of aminopropyl groups during the biosynthesis of polyamines. AdoMet is synthesized from L-methionine and ATP by AdoMet-synthetase. In silico analysis of the P. chrysogenum genome revealed the presence of a single gene (Pc16g04380) encoding a putative protein with high similarity to well-known AdoMet-synthetases. Due to the essential nature of this gene, functional analysis was carried out using RNAi-mediated silencing techniques. Knock-down transformants exhibited a decrease in AdoMet, S-adenosyl-L-homocysteine (AdoHcy), spermidine and benzylpenicillin levels, whereas they accumulated a yellow-orange pigment in submerged cultures. On the other hand, overexpression led to reduced levels of benzylpenicillin, thereby suggesting that the AdoMet synthetase, in addition to participate in primary metabolism, also controls secondary metabolism in P. chrysogenum. Full article

Essential oils (EOs) are well-known for their beneficial properties against a broad range of microorganisms. For the better understanding of their mechanism of action in fungi, a microarray approach was used in order to evaluate the gene expression of Penicillium chrysogenum (recently renamed P. rubens) exposed to the indirect contact (vapors) of eight EOs. The selection of assayed EOs was based on their antifungal activity. The extraction of RNA and the microarray hybridization procedure were optimized for the analysis of P. rubens. Gene ontology annotation was performed to investigate the functional analysis of the genes. To uncover the metabolic pathway of these differentially expressed genes, they were mapped into the KEGG BRITE pathway database. The transcriptomic analysis showed that, from a total of 12,675 genes, only 551 genes are annotated, and the other 12,124 genes encoded hypothetical proteins. Further bioinformatic analysis demonstrated that 1350 genes were upregulated and 765 downregulated at least with half (four) of the utilizing EOs. A microarray investigation has confirmed the main impact of EOs to metabolic processes in P. rubens involved in vital functions. Presumably, this is the first time that a microarray hybridization analysis was performed in order to evaluate the gene expression of P. rubens exposed to various EOs. Full article