In the 1950s, cephalosporin C, a ?-lactam type natural antibiotic, was discovered from a Cephalosporium (nowadays Acremonium) species obtained off the Sardinian coast [25,26]. Cephalosporin C represents the first fungal antibiotic from a marine environment.
A prime example for marine fungal natural products as drugs is the discovery of the ?-lactam antibiotic cephalosporin C, which was further developed by semi-synthetic approaches: its producer, an Acremonium chrysogenum strain, was isolated from seawater samples near a sewer outlet in Sardinia [94]. Although cephalosporin C originally exhibited only weak antibacterial properties, the activity has been gradually increased through the generation of semi-synthetic cephalosporin derivatives [95]. Two-thirds of commercial cephalosporins are derived from biotechnologically-produced cephalosporin C, which serves as a precursor for synthesis of the respective semi-synthetic cephalosporins. After decades of optimisation in fermentation and strain improvement including mutagenesis and genetic engineering (see Section 3.2.3), high-yielding strains of A. chrysogenum reach harvest titres of at least 30 g/L for cephalosporin C in fed-batch fermentations [43]. Consequently, despite cephalosporin C being first isolated as early as 1953 [25,26,96], cephalosporins are still indispensable in antibacterial therapy today, including treatment of methicillin-resistant S. aureus. More than 50 cephalosporins are marketed.
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