Antibiotics: Discovery and Production

What Is an Antibiotic?

An antibiotic is a chemical substance, produced by one microorganism, that is capable of inhibiting the growth of, or directly killing, another microorganism. This ability is, at root, an outcome of natural microbial competition: in the environment, countless different species of bacteria and fungi are constantly competing for the same limited nutrients and space, and producing a chemical that suppresses a rival's growth is, for the producing organism, a competitive advantage. Humans have learned to isolate these naturally evolved chemical weapons and repurpose them as medicines to treat bacterial infections in humans and animals.

The Discovery of Penicillin

The discovery of the first true antibiotic is credited to the Scottish bacteriologist Alexander Fleming, in 1928. While studying colonies of the bacterium Staphylococcus growing on culture plates in his laboratory, Fleming noticed that one particular plate had become accidentally contaminated with a mould. Around the mould colony, he observed a clear zone in which the surrounding bacterial growth had been inhibited -- the bacteria simply were not growing in the area close to the mould. Fleming identified the contaminating mould as Penicillium notatum, and correctly reasoned that it must be releasing some substance into its surroundings capable of killing or inhibiting the nearby bacteria; he named this substance penicillin. Although this was a landmark observation, Fleming himself was unable to isolate, purify or produce penicillin in a form stable and concentrated enough for clinical use. That crucial next step was achieved over a decade later, during the Second World War, by the biochemist Ernst Chain and the pathologist Howard Florey, whose research team developed the methods needed to extract, purify and mass-produce penicillin as a practical, life-saving drug. In recognition of this combined achievement, Fleming, Chain and Florey jointly received the Nobel Prize in Physiology or Medicine in 1945.

How Antibiotics Are Produced Commercially Today

The commercial production of antibiotics such as penicillin follows the same fundamental large-scale fermentation approach used for other industrial microbial products, described earlier in this chapter, but tuned specifically to maximise antibiotic yield:

1. A high-yielding strain of the producing organism (for penicillin, an industrially improved strain of Penicillium chrysogenum -- selected over decades to produce far more antibiotic than Fleming's original P. notatum isolate) is grown in a small starter culture.
2. This starter culture is used to inoculate a large industrial fermenter containing a carefully formulated nutrient medium, typically rich in an appropriate carbon source along with nitrogen and other required nutrients.
3. The fermenter is maintained under tightly controlled conditions of temperature, pH, and aeration (for aerobic producer organisms) for several days, during which the microorganism grows and, in doing so, secretes the antibiotic compound into the surrounding broth. …