The Natural Penicillins — Benzylpenicillin (Penicillin G) and Phenoxymethylpenicillin (Penicillin V)

Abstract

The two so-called natural penicillins are both produced biosynthetically from Penicillium chrysogenum by fermentation. Benzylpenicillin (penicillin G) is formed if phenylacetic acid is added to the culture medium and Phenoxymethylpenicillin (penicillin V) is formed when phenoxyacetic acid is added. Deacylation of penicillin G is brought about by amidase enzymes of bacterial origin which split off the side chain leaving the ‘penicillin nucleus’ or 6-aminopenicillanic acid (6-APA). The ‘new’ or semi-synthetic penicillins (section 4) are derived by grafting different side chains onto 6-APA so conferring widely differing pharmacological and antibacterial properties. The 6-APA nucleus itself consists of a thiazolidine ring fused to a β-lactam ring. This structure is converted into bacteriologically inert penicilloic acid by the enzyme β-lactamase or penicillinase which splits open the β-lactam ring (fig. 1). Some of the semisynthetic penicillins possess bulky side chains which by stearic hindrance mechanisms protect the β-lactam ring from penicillinase; both of the natural penicillins and semisynthetic penicillins such as ampicillin which possess less heavy side chains, remain entirely vulnerable to penicillinase action.