Acremonium chrysogenum

The ancestral strain of Acremonium chrysogenum (at that time called Cephalosporium acremonium) was isolated on the Sardinian coast in 1945 following an observation that the local sewage outlet into the sea cleared at a quite remarkable rate. Advances were slow because the activity was associated with a number of different types of compound. Cephalosporin C was first isolated in 1952, but it was a further decade before clinically usefiil semisynthetic cephalosporins became available. 

Also at Oxford, Abraham and Newton discovered the first cephalosporin, cephalosporin C, as a product of Acremonium chrysogenum (Cephalosporium acremonium).17 This new, sulfur-containing antibiotic was also a (5-lactam but the fused, sulfur-containing ring is a six-membered dihydrothiazine. 

DeModena.J., Gutierrez,S., Velasco, J., Fernandez, F., Fachini,R.,Galazzo,J. Hughes, D. (1993). The production of cephalosporin C by Acremonium chrysogenum is improved by the intracellular expression of a bacterial hemoglobin. Biotechnology, 11, 926-8. 

Menzel et al. [19] Glucose Ethanol Phosphate Saccharomyces cerevisiae, Acremonium chrysogenum and recombinant baby hamster kidney (rBHK) cell cultivations Co-immobilised glucose oxidase and peroxidase Co-immobilised alcohol oxidase and peroxidase Co-immobilised nucleoside phosphorylase, xanthin oxidase and peroxidase Potentiometric, fluoride sensitive (pF), buffer capacity insensitive electrolyte isolator semiconductor capacitor (pF-EIS-CAP) chip ... 

Cephalosporin C (Figure 7.37) is produced commercially by fermentation using cultures of a high-yielding strain of Acremonium chrysogenum (formerly Cephalosporium acremonium). Initial studies of the antibiotic compounds synthesized by C. acremonium identified penicillin N (originally called cephalosporin N) as the major component, with small amounts of cephalosporin C. In contrast to the penicillins, cephalosporin C was stable under acidic conditions and also was not attacked by penicillinase ((5-lactamase). Antibacterial activity was rather low, however, and the antibiotic was poorly absorbed after oral administration. However, the structure offered considerable scope for side-chain modifications, more so than with the penicillins since it has two side-chains, and this has led to a wide variety of cephalosporin drugs, many of which are currently in clinical use. As with the penicillins, removal of the amide... 

W Kallow, H von Dohren, H Kleinkauf. Penicillin biosynthesis energy requirement for tripeptide precursor formation by delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Acremonium chrysogenum. Biochemistry 37 5947-5952, 1998. 

The name of Cephalosporium acremonium has been changed to Acremonium chrysogenum however, Cephalosporium acremonium is used here for historic continuity, since most of the literature contains this name. 

SJ Brewer, JE Farthing, MK Turner. The oxygenation of the 3-methyl group of 7-(3-(5-D-aminoadipamido)-3-methylceph-3-em-4-carboxylic acid (desacetoxycepha-losporin C) by extracts of Acremonium chrysogenum. Biochem Soc Trans 5 1024-1026, 1977. 

K Matsuyama, H Matsumoto, A Matsuda, H Sugiura, KI Komatsu, S Ichikawa. Purification of acetyl coenzyme A deacetylcephalosporin C O-acetyl transferase from Acremonium chrysogenum. Biosci Biotechnol Biochem 56 1410-1412, 1992. 

J Velasco, S Gutierrez, S Campoy, JF Martin. Molecular characterization of the Acremonium chrysogenum cefG gene product the native deacetylcephalosporin C acetyltransferase is not processed into subunits. Biochem J 337 379-385, 1999. 

S Gutierrez, J Velasco, AT Marcos, FJ Fernandez, F Fierro, JL Barredo, B Diez, JF Martin. Expression of the cefG gene is limiting for cephalosporin biosynthesis in Acremonium chrysogenum. Appl Microbiol Biotechnol 48 606-614, 1997. 

J Velasco, S Gutierrez, FJ Fernandez, AT Marcos, C Arenos, JF Martin. Exogenous methionine increases levels of mRNAs transcribed from pcbAB, pcbC, and ce/EF genes, encoding enzymes of the cephalosporin biosynthetic pathway, in Acremonium chrysogenum. J Bacteriol 176 985-991, 1994. 

On-line and Off-line Monitoring of the Production of Cephalosporin C by Acremonium chrysogenum... 

Keywords. Cephalosporin C, Acremonium chrysogenum Extracellular components, Intracellular components,Enzyme activities of biosynthesis, Bottleneck of biosynthesis... 

In the present paper the process monitoring of cephalosporin C (CPC) formation by Acremonium chrysogenum in laboratory investigations are considered. The goal of these investigations was the identification of bottlenecks in the biosynthesis and the improvement of process performance by maximizing the product concentration and yield coefficient and by minimizing the byproducts, which impair the product purification. 

Deacetylcephalosporin C-Acetyltransferase Fig. 1. Biosynthesis of Cephalosporin C in Acremonium chrysogenum... 

Fig. 4. Separation of the four main products appearing during the cultivation of Acremonium chrysogenum at 220 nm...

Fig. 8. Comparison of the detected enzyme activities during the cultivation of Acremonium chrysogenum...

Adinarayana, K., Prabhakar, T., Srinivasulu, V., Rao, A. M., et al. (2003a). Optimization of process parameters for cephalosporin C production under solid state fermentation from Acremonium chrysogenum. Process Biochem. 39,171-177. 

Ullan, R.V., Gasqueiro, j., Banuelo, O., Fernandez, F. j., Gutierrez, S., Martin, j. F., A novel epimerization system in fungal secondary metabolism involved in the conversion of isopenicillin N into penicillin N in Acremonium chrysogenum, J. Biol. Chem. 2002, 277, 46216-46225. 

Cephalosporium acremonium has been reclassified by Gams, who suggested the name Acremonium chrysogenum [106]. 

Diez B, Mellado E, Fouces R, Rodriguez M, Barredo JL. Recombinant Acremonium chrysogenum strains for the industrial production of cephalosporin. Microbiologia 12(3) 359-370, 1996. 

Karaffa L, Sandor E, Kozma J, Kubicek CP, Szentirmai A. The role of the alternative respiratory pathway in the stimulation of cephalosporin C formation by soybean oil in Acremonium chrysogenum. Appl Microbiol Biotechnol 51 (5) 633 —638, 1999. 

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