Antibiotics are our mainstay in the battle against bacterial infections, despite often rapid rates of resistance development. β-lactam antibiotics are a class of antimicrobial that all contain a β-lactam ring in their structure. The first β-lactam antibiotic, penicillin, was famously discovered by accident by Alexander Fleming when Penicillium notatum contamination of his Staphylococcus plates caused clear zones around the mould growth to form. The mould had secreted a substance that inhibited bacterial growth. Penicillin is a secondary metabolite of the Penicillium species.
Since its first medical use in 1941, it has saved millions of lives and β-lactams are now the most economically important of all the groups of antimicrobials. Penicillin’s mechanism of action involves the inhibition of peptidoglycan cross-links in bacterial cell walls. This leads to an imbalance between cell wall production and degradations, causing the cell to rapidly die.
Penicillins, semi-synthetic penicillins and other β-lactams are active against a range of different bacteria including Gram-positive bacteria such as Streptococci, β-lactamase positive Gram-positive bacteria such as Staphylococcus and Gram-negative organisms including Neisseria spp.
Penicillin and other β-lactam antibiotics are secondary metabolites, meaning that they are produced in the late stationary phase and are not involved in normal growth, development or reproduction of the organism . Modern day penicillin is a secondary metabolite of Penicillium chrysogenum rather than P.notatum due to its significantly higher yield. Batch fermentation production of penicillin is carried out in large stainless steel tanks up to 100,000 gallons in capacity and a ‘batch fill’ and a withdraw system is used to replenish the tank with fresh sterile medium.
Penicillin is excreted into the medium but the antibiotics in the fermenter will be dilute and impure. Downstream processing of the penicillin involves filtration and chemical purification. These processes are expensive and can account for 50% of the total cost! The resulting penicillin (penicillin G) can be modified to create a variety of semi-synthetic penicillins with different properties and activity against different microorganisms.
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