INDUCTION OF CEPHALOSPORIN C IN Cephalosporium acremonium USING U.V. LIGHT AND SELECTION OF A MUTANT THAT SHOWED HIGHEST FERMENTATION CAPABILITY (original) (raw)
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Pakistan Journal of Zoology
In the present study, cephalosporin was produced through submerged fermentation in 250 ml Erlenmeyer flask. About one hundred fungal strains were isolated and screened for maximum productivity of the antibiotic cephalosporin. Among these, the strain IIB-10 identified as Acremonium chrysogenum was found to have maximum production of cephalosporin when cultivated on M-4 medium containing (%, w/v): Corn meal, 2; Baker's flour, 1.5; Ammonium sulphate, 0.1; Calcium carbonate, 0.3 and Methyl oleate, 1.6. The nutritional study for maximum cephalosporin productivity was undertaken. Sucrose as a sole carbon source at 2.5% level, peptone at a concentration of 1.5% as an organic nitrogen source and Ammonium sulphate at a concentration of 0.4% as an inorganic nitrogen source supported maximum production of cephalosporin i.e., 721.89 mg/l.
Genetic engineering approach to reduce undesirable by-products in cephalosporin C fermentation
Journal of Industrial Microbiology and Biotechnology, 1998
Deacetoxycephalosporin C (DAOC) is produced by Acremonium chrysogenum as an intermediate compound in the cephalosporin C biosynthetic pathway, and is present in small quantities in cephalosporin C fermentation broth. This compound forms an undesirable impurity, 7-aminodeacetoxycephalosporanic acid (7-ADCA), when the cephalosporin C is converted chemically or enzymatically to 7-aminocephalosporanic acid (7-ACA). In the cephalosporin C biosynthetic pathway of A. chrysogenum, the bifunctional expandase/hydroxylase enzyme catalyzes the conversion of penicillin N to DAOC and subsequently deacetylcephalosporin C (DAC). By genetically engineering strains for increased copy number of the expandase/hydroxylase gene, we were able to reduce the level of DAOC present in the fermentation broth to 50% of the control. CHEF gel electrophoresis and Southern analysis of DNA from two of the transformants revealed that one copy of the transforming plasmid had integrated into chromosome VIII (ie a heterologous site from the host expandase/hydroxylase gene situated on chromosome II). Northern analysis indicated that the amount of transcribed expandase/hydroxylase mRNA in one of the transformants is increased approximately twofold over that in the untransformed host.
Optimal feeding strategy of Cephalosporin C fermentation
IOP Conference Series: Materials Science and Engineering
Cephalosporin C is a β-lactam type of antibiotic produced from the fungus Acremonium chrysogenum through fermentation process, either by batch or fed-batch mode. Cephalosporin represents the bulk majority of antibiotic production due to its enhanced antibacterial spectrum against gram positive and gram negative bacterial strains relating to diseases and infections in the skin, respiratory system, and urinary tract. In the production process, it is crucial to maximize the yield of antibiotic produced, since the major costs of production come from the fermentation and recovery of the antibiotic. To address this issue, an effective feeding strategy of the culture producing the target antibiotic is very important to achieve high yield and avoid undesired production of other metabolites, which reduce the yield of desired metabolite. The latter can add extra cost to recovery and purification of the desired metabolite. This paper presents an optimal strategy for the fed-batch fermentation process producing Cephalosporin C (CPC) from the fungus A. chrysogenum by optimization of the substrate feeding flow rate. The preferred substrates are glucose and sucrose as the fungus possesses diauxic behaviour in the presence of the two carbon sources. It is shown that a twostep fed-batch feeding of glucose results in a significantly higher antibiotic production than a batch mode or single-step fed-batch feeding strategy.
Process strategies for cephalosporin C fermentation
JOURNAL OF SCIENTIFIC …, 2006
Cephalosporin C (CPC), a β-lactam antibiotic, is starting molecule for industrial production of semi synthetic cephalosporins. CPC fermentation has been carried out in Air Lift Reactor (indigenously made up of borosilicate glass) in different fermentation modes ie, batch and fed batch ...
A high throughput screening (HTS) strategy was investigated for screening high-yielding cephalosporin C (CPC) using mutated Cephalosporium acremonium. The strategy was based on microtiter plates (MTPs) to culture the microorganisms and measure its products. The feasibility of MTPs was to replace the cultivation in shake flasks, and CPC production will be determined using turbidimetric assay by ELISA reader to replace HPLC assay. The HTS systems were verified by screening high-producing CPC mutants. By using this HTS strategy, two mutants, i.e. 5-A1 and 8-A2 were selected from the secondary mutagenesis. The volumetric productivity of Cephalosporin C from Cephalosporium acremonium was 7914.43 U/ml; 8639.24 U/ml in shake flasks. CPC production was improved about 246% and 269% compared with that of original strain.
Journal of Molecular Microbiology and Biotechnology, 2012
Despite the importance of Acremonium chrysogenum as the only cephalosporin C (CPC) producer, there is still a limited understanding about the molecular mechanisms regulating antibiotic biosynthesis in this fungus. Based on the previously described relationship between environmental pH and antibiotic production in numerous filamentous fungi, we studied the expression of genes related to CPC production in A. chrysogenum . We report for the first time similarities and differences, characterizing CPC production by A. chrysogenum under a variable pH environment, in submerged and solid-state fermentation. This characterization is supported by measurements of parameters, like CPC production, pH, growth, and expression levels of several genes involved, directly or indirectly, in CPC production. Interesting differences in intermediate (Pen N) and certain biosynthetic gene expression levels were observed. Our results point out some relationships between physiological features and gene expression that open important improvement perspectives for both culture systems.
Influence of Medium Constituents on the Biosynthesis of Cephalosporin-C
Electronic Journal of …, 2007
Cephalosporins together with penicillin belong to the family of β-lactam antibiotics. Cephalosporins are important broad-spectrum antibiotics in the international market and are more resistant to β-lactamases than penicillins. Cephalosporin-C (CPC), the starting material used for the ...